DEVICE AND METHOD FOR SELECTIVELY AND REVERSIBLY MODULATING A STRUCTURE OF THE NERVOUS SYSTEM IN ORDER TO INHIBIT PAIN

Abstract

The present invention relates to a system and method for selectively and reversibly modulating targeted nervous or non-nervous tissue of a nervous system for the treatment of pain. Electrical stimulation is delivered to the treatment site which selectively and reversibly modulates the targeted nervous or non-nervous tissue of the nervous structure, inhibiting pain while preserving other motor and motor functions and proprioception.

Description

Title of the invention: Device and method for selectively and reversibly modulating a structure of the nervous system in order to inhibit pain CROSS REFERENCE TO RELATED REQUESTS

[0001] This application claims priority over U.S. Provisional Application No. 62 / 776,908, filed on Friday, December 7, 2018. Technical field

[0002] The present invention relates generally to a device and method for modulating the activity of nervous and non-nervous tissues to treat pain. In particular, the invention relates to a device and method for selectively and reversibly modulating nervous or non-nervous tissue of a nervous structure to inhibit pain while preserving other sensory and motor functions, as well as proprioception. CONTEXT OF THE INVENTION

[0003] Pain can be treated by both destructive and non-destructive methods by disrupting the transmission of pain signals from the body to the brain. Destructive methods are commonly used to treat chronic pain indications and include thermal ablation, cryoablation, chemical ablation (e.g., using phenols, lidocaine, Botox™, ultrasound ablation, and mechanical transection). However, destruction of the nerve structure results in an immediate loss of nerve functionality and may lead to long-term atrophy, neuropathy, and ultimately increased pain. In addition, mixed nerves and ganglia are not typically targeted for destructive interventions for chronic pain due to the desire to maintain motor and non-pain sensory function.Furthermore, destruction of a nerve structure does not promote postoperative and perioperative pain management, in which it is desirable to preserve motor and non-pain sensory function. Therefore, destructive methods of disrupting pain signals are generally not used for acute pain applications such as postoperative pain.

[0004] Non-destructive methods of treating pain include the use of prescription pain medications (e.g., opioids), injections of local anesthetics, topical or injected cocktails including steroids and other anti-inflammatory agents, continuous infusion of local anesthetics, electrical blockade, electrical stimulation, and application pulsed radiofrequency energy. Each of these methods presents a unique set of challenges that compromise the effectiveness and ease of use of the treatment. For example, prescription pain medications cause unwanted side effects and can lead to addiction. Meanwhile, injections of local anesthetics and cocktails have a short effective duration of only a few hours, while continuous infusion of anesthetics requires an external device to be attached to the patient for long-term treatment (days). In addition, the use of local anesthetics poses a risk of nerve toxicity, vascular toxicity, and allergic reactions.Finally, these agents are not selective with respect to the type of nerve activity they block (e.g., they block both nerve fiber activity associated with pain and nerve fiber activity associated with motor function).

[0005] Electrical neuromodulation techniques have a lower risk of side effects than chemical interventions and allow for adjustable and local pain management. However, existing electrical blockade technologies are only used to treat chronic post-amputation pain and require implantation of an internal pulse generator and nerve cuff into the patient for long-term blockade. As such, the need for surgical implantation places a heavy burden on the use of electrical blockade for acute pain applications in small and large nerves, as well as electrical blockade of acute pain to the head and face.Furthermore, although electrical stimulation devices are commonly used to alleviate pain, their effectiveness has not been sufficient to date for managing moderate to severe pain levels, such as those experienced by a patient with severe or chronic migraine, perioperative pain, and / or postoperative pain in the days or weeks following surgery. Electrical nerve stimulation devices have also been used in peripheral nerves, dorsal root ganglia, and the spinal cord for the treatment of chronic pain. However, they all require surgical implantation and may unintentionally activate motor fibers or sensory pain fibers when applied to mixed nerves or ganglia.Furthermore, although radiofrequency energy treatment is procedure-based and the patient is not bothered by a take-home device, it cannot be used to treat large nerves and treatment results are inconsistent for small nerves. In addition, the selectivity and time to reversal of radiofrequency energy treatment for acute pain are unknown.

[0006] As such, there is a need for an electrical device and method capable of temporarily and selectively inhibiting pain by modulating neural activity and non-neural in small and large diameter peripheral nerves, cranial nerves, ganglia, autonomic nerves, plexuses and the spinal cord, with effects lasting from several days to several weeks, when temporary and selective blockade does not pose a risk of neural toxicity, vascular toxicity or allergy. Summary of the invention

[0007] The present invention relates to a system and method for selectively and reversibly modulating targeted nervous or non-nervous tissue of a nervous system for the treatment of pain. Electrical stimulation is delivered to the treatment site which selectively and / or reversibly modulates the targeted nervous or non-nervous tissue of the nervous structure, inhibiting pain while preserving other sensory and motor functions, as well as proprioception. In one aspect, the invention provides a system for selectively and / or reversibly modulating targeted nervous or non-nervous tissue of a structure of the nervous system (e.g., to treat a pathological condition of a patient). The system comprises an electrical stimulation device comprising one or more electrodes (e.g., having a size configuration,of suitable shape and contact surface area for delivering electrical stimulation to the nervous system structure) (e.g., unipolar or bipolar) (e.g., a single electrode or an electrode array) that delivers electrical stimulation at a treatment site located proximate to the targeted nervous and non-nervous tissue of the nervous system structure; and a controller configured to connect to one or more electrodes of the electrical stimulation device and to a power source for providing electrical energy to the one or more electrodes, the controller being configured to direct operation of the electrical stimulation device (e.g., controlled as a function of current, voltage, power, and / or temperature) and apply the electrical stimulation at the treatment site through the electrode,and the application of electrical stimulation at the treatment site modulating the targeted nervous or non-nervous tissue inhibiting pain and preserving other sensory and motor functions, as well as proprioception.

[0008] In some embodiments, the pain comprises at least one of acute pain, post-operative pain, neuropathic pain, chronic pain, and head and face pain.

[0009] In some embodiments, a single application of electrical stimulation at the treatment site selectively modulates the targeted nervous or non-nervous tissue, resulting in subsequent inhibition of pain (e.g., for a period of about 1 day to about 30 days, for a period from about 30 days to about 60 days, for a period of about 60 days to about 90 days, for a period of about 90 days to about 120 days, for a period of about 120 days to about 150 days, for a period of about 150 days to about 180 days, for a period of about 180 days to about 270 days, for a period of about 270 days to about 365 days) (e.g., where the pain is chronic pain, a single application of the electrical stimulation at the treatment site selectively modulates the targeted nervous or non-nervous tissue, resulting in subsequent inhibition of pain for a period of about 90 days to about 365 days).

[0010] In some embodiments, the single application of electrical stimulation at the treatment site selectively modulates the targeted nervous or non-nervous tissue, resulting in the subsequent inhibition of pain for a period of about 5 days to about 30 days.

[0011] In some embodiments, the application of electrical stimulation at the treatment site modulates (e.g., selectively modulates and / or reversibly modulates) the targeted nervous or non-nervous tissue inhibiting nerve signal transmission by nerve fibers that are responsible for pain transmission (e.g., and for transmission of thermoception, autonomic activity, and visceral function), wherein nerve signal transmission by the nerve fibers is responsible for other sensory and motor functions, proprioception is preserved, and wherein the other sensory function is selected from the group consisting of touch, vision, hearing, taste, smell, and balance.

[0012] In some embodiments, the one or more electrodes are configured (e.g., with an appropriate size and shape) to be positioned adjacent to the nervous system structure comprising at least one of a peripheral nerve, a cranial nerve, a ganglion and an autonomic nerve, a plexus, and the spinal cord (e.g., wherein the ganglion comprises at least one of a dorsal root ganglion, a sympathetic ganglion, a parasympathetic ganglion, a sphenopalatine ganglion, a gasserian ganglion).

[0013] In some embodiments, the nervous system structure comprises a nerve or ganglion (e.g., a cranial nerve, an autonomic nerve, a plexus, and the spinal cord) having a diameter greater than about 2.5 mm, the or at least one of the electrodes having a size and shape and contact area configuration (e.g., an area ranging from 1 mm2 to about 100 mm2) sufficient to deliver electrical stimulation to the nerve or ganglion (e.g., the controller being configured to generate an appropriate waveform forming the electrical stimulation to modulate (e.g., selectively modulate or demodulate) the electrical stimulation. reversibly) the target nervous or non-nervous tissue of the nervous system structure).

[0014] In some embodiments, the application of electrical stimulation at the treatment site selectively inhibits nerve signal transmission by at least one of a myelinated Aδ fiber and an unmyelinated C fiber disposed in the peripheral nerve while preserving nerve signal transmission by at least one of the Aδ and Aδ fibers, and / or the motor fibers.

[0015] In some embodiments, applying the stimulation at the treatment site selectively inhibits nerve signal transmission by at least one of a myelinated Aδ fiber and an unmyelinated C fiber disposed in the peripheral nerve while preserving nerve signal transmission by at least one of Aδ and Aα fibers, and / or motor fibers of a neighboring nerve or nerve fascicle.

[0016] In some embodiments, the controller is adjustable to vary the electrical stimulation (e.g., a parameter of the electrical stimulation) based on measured feedback selected from the group consisting of: measured inhibition of nerve signal transmission, measured temperature (e.g., at the treatment site, at the electrode(s) or portion thereof, on the electrical stimulation device, on the patient's skin), patient input (e.g., pain input), feedback corresponding to at least one of the adjustable parameters of the electrical stimulation, a treatment setting associated with a recovery time, contact impedance of the electrode, an electric field generated in the tissue, a physiological response of the patient (e.g., blood flow, skin conductance, heart rate, muscle activity (e.g.,electromyography)) and a combination of these.

[0017] In some embodiments, the controller is configured to vary the duty cycle and / or the duration of the wave envelope of the electrical stimulation in real time to maximize the voltage delivered to the tissue, without exceeding the temperature of the target tissue at the treatment site (e.g., modulating the stimulation duty cycle and / or the stimulation envelope to maximize the voltage without exceeding a destructive tissue temperature at the treatment site).

[0018] In some embodiments, the controller is configured to vary the duty cycle and / or the duration of the wave envelope of the electrical stimulation in real time to maximize the current delivered to the tissue, without exceeding the temperature of the target tissue at the treatment site (e.g., modulating the stimulation duty cycle or the stimulation envelope to maximize the current without exceeding a destructive tissue temperature at the treatment site).

[0019] In some embodiments, the controller is adjustable to vary at least one parameter of the electrical stimulation to modulate (e.g., selectively inhibit and / or reversibly inhibit) nerve signal transmission via i) at least one of myelinated Aδ fibers and / or unmyelinated C fibers or ii) a large nerve or ganglion or neural structure (e.g., cranial nerve, ganglion, autonomic nerve, plexus, spinal cord, dorsal root ganglion, sympathetic ganglion, parasympathetic ganglion, sphenopalatine ganglion, gasserian ganglion), wherein at least one parameter is selected from the group consisting of a waveform, a wave frequency, a wave amplitude, a wave envelope duration, an electric field strength generated at the electrode (e.g., measured at the electrode or treatment site),a DC wave shift, a wave duty cycle, a tissue temperature, a cooling mechanism parameter (e.g., a cooling rate, a cooling fluid flow rate, a cooling medium pressure, a temperature measured at the treatment site or at a portion of the cooling mechanism), and a treatment duration.

[0020] In some embodiments, the nervous system structure comprises a peripheral nerve, wherein the controller is adjustable to apply electrical stimulation to differentially inhibit the function of myelinated Aδ fibers or nerve fibers responsible for a sharp / shooting pain sensation (e.g., Aδ fibers and / or nerve fibers responsible for a sharp / shooting pain sensation have a higher percentage of inhibited fibers than unmyelinated C fibers or nerve fibers responsible for a dull / sharp pain sensation).

[0021] In some embodiments, the nervous system structure comprises a peripheral nerve, wherein the controller can be adjusted to apply electrical stimulation to differentially inhibit the function of unmyelinated C-fibers or nerve fibers responsible for a dull / hyperacute pain sensation (e.g., unmyelinated C-fibers and / or nerve fibers responsible for a dull / hyperacute pain sensation have a higher percentage of inhibited fibers than myelinated A-fibers).

[0022] In some embodiments, the controller is adjustable to vary at least one parameter of the electrical stimulation to modulate (e.g., selectively and / or reversibly modulate) nerve signal transmission in a portion of the nervous system structure having a cross-section transverse less than or equal to the complete section of the structure of the nervous system.

[0023] In some embodiments, the controller is adjustable to vary at least one parameter of the electrical stimulation to reduce an initial response of the nervous system structure and / or an activation of the nervous system structure at the onset of inhibition of the nervous system structure.

[0024] In some embodiments, the controller is adjustable to deliver electrical stimulation to the treatment site having a frequency selected from the group consisting of about 100 kHz, about 200 kHz, about 300 kHz, about 400 kHz, about 500 kHz, about 600 kHz, about 700 kHz, about 800 kHz, about 900 kHz, and about 1 MHz.

[0025] In some embodiments, the electrical stimulation delivered to the treatment site has an amplitude range of between about 5 mA (e.g., peak to center, corresponding to 10 mA peak to peak) and about 1.25 A (peak to center, corresponding to 2.5 A peak to peak).

[0026] In some embodiments, the electrical stimulation delivered to the treatment site has an amplitude range of about 10 V to about 500 V (peak to center, corresponding to 20 to 1000 V peak to peak).

[0027] In some embodiments, the electrical stimulation delivered to the treatment site has a power range of between about 0.1 W and about 1250 W.

[0028] In some embodiments, the electrical stimulation delivered to the treatment site generates or induces an electric field strength at the target site and / or an electrode of between about 20 kV / m and about 2000 kV / m.

[0029] In some embodiments, the electrical stimulation delivered to the treatment site has a waveform component (e.g., a continuously delivered wave or an intermittently delivered wave (e.g., pulsed for a predefined duration)) (e.g., as a charge-balanced wave or as a non-charge-balanced wave), including at least one of a sine wave, a square wave, a triangle wave, a pulse wave, a shape-modulated wave, a frequency-modulated wave, an amplitude-modulated wave that provides a continuous delivery of electrical stimulation (e.g., a chirp) at the treatment site, and a combination (e.g., an additive combination) thereof.

[0030] In some embodiments, the electrical stimulation delivered to the treatment site has a duty cycle of between about 0.1% and about 99%.

[0031] In some embodiments, the electrical stimulation delivered to the treatment site has an inter-pulse width of between about 1 ms and about 999 ms.

[0032] In some embodiments, the electrical stimulation is delivered to the treatment site for a duration of up to 30 minutes.

[0033] In some embodiments, the controller is adjustable to apply the electrical stimulation while maintaining the tissue temperature between about 5°C and about 60°C.

[0034] In some embodiments, the electrical stimulation device includes a device body configured to be implanted into the patient at a location adjacent to the treatment site (e.g., placed or implanted percutaneously).

[0035] In some embodiments, the controller includes a stimulator (e.g., a function or wave generator) (e.g., an external function or wave generator), the stimulator coupled to both the electrode and an interface of the controller, wherein operation of the stimulator is directed by the controller to provide electrical stimulation to the electrode.

[0036] In some embodiments, the electrode comprises an electrode assembly in the form of a paddle, a sleeve, a cylindrical catheter or a needle, a wire or a thin probe.

[0037] In some embodiments, the electrode(s) are sized and / or shaped (e.g., an electrical contact of the electrode has an area ranging from about 1 mm2 to about 100 mm2) to maximize and direct the electric field toward the nervous system structure.

[0038] In some embodiments, the one or more electrodes comprise at least two electrical contacts (e.g., the at least two electrical contacts being configured to be positioned near the nervous system structure during treatment) (e.g., the controller being configured to independently operate (e.g., in a multi-polar manner to direct the current of the resulting electric field) each of the at least two electrical contacts).

[0039] In some embodiments, each of the electrical contacts is located on a single wire, forming a stimulation pair (e.g., a cathode and an anode).

[0040] In some embodiments, each of the electrical contacts has a length of between about 1 and 50 mm (e.g., preferably a length of between about 1 mm and about 30 mm, between about 2 mm and about 20 mm, between about 2 mm and about 15 mm, or about 5 mm and 10 mm).

[0041] In some embodiments, the length of each of the electrical contacts is the same.

[0042] In some embodiments, the length of each of the electrical contacts is different.

[0043] In some embodiments, the at least two electrical contacts com have a distal electrical contact adjacent to a distal end of the electrode and a proximal electrical contact located along the electrode at a location between the distal electrical contact and a proximal end of the electrode, and a length of the distal electrical contact being greater than a length of the proximal electrical contact (e.g., the length of the distal electrical contact may be about 10 mm long and the length of the proximal electrical contact may be about 4 mm long).

[0044] In some embodiments, the one or more electrodes comprise an electrode assembly in the form of an elongated body, the distal end of the elongated body comprising a curvature such that a distal end portion of the elongated body extends at an angle relative to a longitudinal axis of the elongated body, the angle of the distal end portion relative to the longitudinal axis of the elongated body being between about 0 and about 50 degrees (e.g., preferably between about 5 and about 15 degrees).

[0045] In some embodiments, the distal end portion of the elongated body is straight.

[0046] In some embodiments, the distal end portion of the elongated body is curved.

[0047] In some embodiments, the electrode assembly includes at least two electrical contacts including a distal electrical contact provided on the distal end portion of the elongated body and a proximal electrical contact provided along the elongated body between the distal end portion and a proximal end of the electrode assembly.

[0048] In some embodiments, the distal electrical contact is sized and configured to interface with the targeted nervous or non-nervous tissue of the nervous system structure, and the proximal electrical contact is sized and configured to be positioned in subcutaneous tissue (e.g., fat, fascia, muscle).

[0049] In some embodiments, each of the one or more electrodes comprises at least two electrical contacts, each of the electrical contacts being located on a same side of the elongated body of the electrode.

[0050] In some embodiments, the conductive regions of each of the electrical contacts are on the same side of the elongated body and do not deliver electrical energy circumferentially to a portion of a circumference of the elongated body without electrical contacts (e.g., the electrical contact does not deliver electrical energy circumferentially to a short axis of the wire, thereby providing voltage field shaping and current direction).

[0051] In some embodiments, the system further comprises a resistor po electrically located in series with an electrical contact included in the electrode(s).

[0052] In some embodiments, the electrical contacts provided on the one or more electrodes are formed from a higher impedance or high capacitance material.

[0053] In some embodiments, the electrical contacts provided on the one or more electrodes have a smooth curvilinear shaped perimeter.

[0054] In some embodiments, the electrical contacts provided on the one or more electrodes have an oval-shaped perimeter.

[0055] In some embodiments, the electrical contacts provided on the electrode(s) have a rectilinearly shaped perimeter.

[0056] In some embodiments, the system further comprises a temperature measuring device (e.g., a thermocouple, a thermistor) provided on the one or more electrodes to provide a measurement of the temperature of the tissue.

[0057] In some embodiments, at least one of an electrical contact and a temperature measuring device provided on the one or more electrodes is printed from an electrically and thermally conductive material.

[0058] In some embodiments, the electrical contacts provided on the one or more electrodes extend partially around a circumference of the corresponding electrode, an arc length of the electrical contact being less than 180 degrees, such that the electrical contact extends around less than half of the circumference of the electrode.

[0059] In some embodiments, the electrode is electrically coupled to the controller via a circumferentially shaped contact surface provided on the electrode and a corresponding circumferentially shaped contact surface provided on a wire electrically coupled to the controller.

[0060] In some embodiments, the circumferentially shaped contact surface comprises more than one circumferentially shaped contact surface arranged concentrically about the longitudinal axis of the electrode (e.g., four circumferentially shaped contact surfaces of varying diameter), wherein a wire electrically coupled between the electrode and the generator comprises more than one corresponding circumferentially shaped contact surface arranged concentrically about a longitudinal axis of the wire (e.g., four circumferentially shaped contact surfaces of varying diameter).

[0061] In some embodiments, the contact surfaces of the circumferentially shaped electrode are separated by a dielectric layer (e.g., electrically insulating materials and / or air supplied between adjacent conductive surfaces), with the contact surfaces of the circumferentially shaped wire being separated by a dielectric layer. electrical (e.g., electrically insulating materials and / or air provided between adjacent conductive surfaces).

[0062] In some embodiments, the electrical circuit of the electrodes extends within the electrode within the circumferentially shaped contact surface.

[0063] In some embodiments, at least one of the one or more electrodes is a unipolar electrode configured to be positioned on a contact surface of the stimulation device, and a return electrode is positioned on an exterior surface of the patient's skin.

[0064] In some embodiments, the stimulation device is reusable.

[0065] In some embodiments, the stimulation device is disposable.

[0066] In some embodiments, the system further comprises a user interface lizer (including, for example, a display (for example, to provide an indication of the status of the control device, the stimulation device, the patient)), the user interface being configured to receive input from the user, direct the application of electrical stimulation to the treatment site (for example, to vary pain inhibition (while preserving other sensory and motor function and proprioception).

[0067] In some embodiments, the system further includes a display coupled to at least one of the controller and the stimulation device, the display providing an indication of the status of the stimulation device.

[0068] In some embodiments, the system further includes a temperature sensor (e.g., a thermistor, a thermocouple) coupled to the stimulation device to measure a temperature of at least one of i) a contact surface of the stimulation device and ii) patient tissue adjacent to the contact surface or the electrode, the temperature sensor coupled to the controller and providing thermal feedback regarding a measured temperature, the controller adjustable to vary at least one parameter of the electrical stimulation (e.g., by the controller or by the user) in response to thermal feedback received from the temperature sensor (e.g.,to adjust the temperature of the contact surface and maintain the temperature of the patient's tissue below a tissue-destructive temperature and / or to maintain the temperature of the contact surface of the stimulation device below the tissue-destructive temperature).

[0069] In some embodiments, the system further includes a cooling mechanism configured to provide a cooling effect at the treatment site (e.g., the contact surface of the stimulation device), the cooling effect preventing damage (e.g., by pre-cooling or maintenance of temperature when electrical stimulation is delivered) at the treatment site (e.g., preserving patient tissue temperatures below a tissue-destructive temperature).

[0070] In another aspect, the invention provides a method for selectively and reversibly modulating targeted nervous and non-nervous tissue of a nervous system structure with the application of electrical stimulation (e.g., a single application of electrical stimulation) to treat a pathological condition of a patient. The method comprises identifying a targeted nervous system structure; positioning an electrical stimulation device at a treatment site proximate to the targeted nervous and non-nervous tissue of the nervous system structure, the electrical stimulation device comprising an electrode that provides electrical stimulation at the treatment site; delivering electrical stimulation to the treatment site via the electrode;applying electrical stimulation at the treatment site selectively modulating the targeted nervous or non-nervous tissue of the nervous system structure inhibiting pain and preserving other sensory and motor function, as well as proprioception; and applying electrical stimulation at the treatment site selectively modulating the targeted nervous or non-nervous tissue and subsequent inhibition of pain (e.g., for a period of about 1 day to about 30 days, for a period of about 30 days to about 60 days, for a period of about 60 days to about 90 days, for a period of about 90 days to about 120 days, for a period of about 120 days to about 150 days, for a period of about 150 days to about 180 days, for a period of about 180 days to about 270 days, for a period of about 270 days to about 365 days). ;

[0071] In some embodiments, the nervous system structure comprises at least one peripheral nerve, a cranial nerve, a ganglion (e.g., the ganglion comprising at least one of a dorsal root ganglion, a sympathetic ganglion, a parasympathetic ganglion, a sphenopalatine ganglion, a gasserian ganglion, a plexus, the spinal cord), an autonomic nerve, and an autonomic ganglion.

[0072] In some embodiments, the application of electrical stimulation at the treatment site selectively modulates the targeted nervous or non-nervous tissue inhibiting nerve signal transmission through nerve fibers responsible for pain transmission, wherein nerve signal transmission through nerve fibers responsible for other sensory and motor functions, and proprioception is preserved, and the other sensory function includes at least one of touch, vision, hearing, taste, smell, and balance.

[0073] In some embodiments, the pain comprises at least one of acute pain, operative pain, post-operative pain, traumatic pain, neuropathic pain, chronic pain, and head and facial pain.

[0074] In some embodiments, when the pain is acute pain, the electrical stimulation is applied at least immediately before a surgical procedure, intraoperatively, and immediately after a surgical procedure or trauma.

[0075] In some embodiments, the electrical stimulation is delivered to the treatment site more than 24 hours before a surgical procedure.

[0076] In some embodiments, when the pain is post-operative pain following a knee arthroplasty procedure, the electrical stimulation is applied to the femoral nerve, sciatic nerve, obturator nerve, and lateral cutaneous nerve and nerve branches, or a combination thereof.

[0077] In some embodiments, when the pain is shoulder pain, the electrical stimulation is applied to the brachial plexus, the axillary nerve, the suprascapular nerve, and the lateral pectoral nerve, or a combination thereof.

[0078] In some embodiments, when the pain is associated with a medical procedure and / or trauma to the arm and / or hand, the electrical stimulation is applied individually to the medial, ulnar, and radial nerves or the brachial plexus, or a combination thereof.

[0079] In some embodiments, when pain is associated with a medical procedure and / or trauma to the ankle and / or foot, electrical stimulation is applied to the tibial, peroneal / sural, and saphenous nerves, or a combination thereof.

[0080] In some embodiments, when pain is associated with hip arthroplasty, electrical stimulation is applied to the femoral, sciatic, or obturator nerves (e.g., a common obturator nerve before it branches into anterior and posterior nerves) and / or a plexus, or a combination thereof.

[0081] In some embodiments, when pain is associated with anterior cruciate ligament (ACL) repair, electrical stimulation is applied to the femoral or sciatic nerve, or a combination thereof.

[0082] In some embodiments, the pain is neuropathic pain or chronic pain, electrical stimulation is used to deliver a therapeutic treatment bolus on demand.

[0083] In some embodiments, the step of positioning the electrical stimulation device proximate the treatment site comprises: positioning the electrode proximate the nervous system structure percutaneously through an opening in the patient's skin; or implanting the electrode in the patient at a location adjacent to the treatment site.

[0084] In some embodiments, the step of positioning the electrical stimulation device proximate the treatment site further comprises: delivering an initial electrical stimulation to the treatment site via the electrode; measuring at least one of a voltage and a current on the electrode; and adjusting a position of the electrode at the treatment site until the measured voltage and current correspond to a threshold voltage and a threshold current, respectively.

[0085] In some embodiments, the method further comprises adjusting at least one parameter of the electrical stimulation to selectively inhibit transmission of the nerve signal by the targeted nervous or non-nervous tissue, the at least one parameter being selected from the group consisting of a waveform, a wave frequency, a wave amplitude, a wave envelope duration, an electric field strength generated at the electrode (e.g., measured at the electrode or the treatment site), a DC wave offset, a wave duty cycle, a tissue temperature, a cooling mechanism parameter (e.g., a cooling rate, a flow rate of the cooling fluid, a pressure of the cooling medium, a temperature measured at the treatment site or at a portion of the cooling mechanism), and a treatment duration.

[0086] In some embodiments, the method further includes modulating the duty cycle or wave envelope duration of the electrical stimulation in real time to maximize the voltage delivered to the treatment site without exceeding a temperature of the target tissue at the treatment site (e.g., modulating the stimulation duty cycle or stimulation envelope to maximize the voltage without exceeding a tissue-destructive temperature at the treatment site).

[0087] In some embodiments, the method further comprises modulating the duty cycle or wave envelope duration of the electrical stimulation in real time to maximize the current delivered to the treatment site without exceeding a temperature of the target tissue at the treatment site (e.g., modulating the stimulation duty cycle or stimulation envelope to maximize the current without exceeding an irreversibly tissue-destructive temperature).

[0088] In some embodiments, the method further comprises gradually increasing the stimulation amplitude of the electrical stimulation to an amplitude plateau.

[0089] In some embodiments, the method further comprises adjusting the controller to vary the electrical stimulation based on measured feedback selected from the group consisting of: measured inhibition of the transmission of the nerve signal, the measured temperature (e.g. at the treatment site, at the electrode(s) or part thereof, on the electrical stimulation device, on the patient's skin), a patient input (e.g. a pain input), feedback corresponding to at least one of the adjustable parameters, a treatment setting associated with a recovery time, a contact impedance of the electrode, an electric field generated in the tissue, a physiological response of the patient (e.g. blood flow, skin conductance, heart rate, muscle activity (e.g. electromyography)) and a combination thereof.

[0090] In some embodiments, the electrode includes a first and a second electrode that operate independently, wherein delivering electrical stimulation to the treatment site via the electrode further includes providing a first electrical stimulation via the first electrode and delivering a second electrical stimulation via the second electrode, wherein the first and second electrical stimulations are delivered intermittently, wherein the first electrical stimulation is alternated with respect to the second electrical stimulation such that an on cycle of the first electrical stimulation occurs during an off cycle of the second electrical stimulation and an on cycle of the second electrical stimulation occurs during an off cycle of the first electrical stimulation.

[0091] In some embodiments, the method further includes measuring, at a temperature sensor (e.g., a thermistor, a thermocouple), a temperature of at least one of a contact surface of the stimulation device and patient tissue adjacent to the contact surface during delivery of the electrical stimulation, the temperature sensor providing thermal feedback regarding a measured temperature to the stimulation device; and adjusting the electrical stimulation (e.g., adjusting a parameter of the electrical stimulation) in response to the thermal feedback received from the temperature sensor to create a cooling effect on at least one of the contact surface of the stimulation device and patient tissue adjacent to the contact surface.

[0092] In some embodiments, the method further comprises measuring, at a temperature sensor (e.g., a thermistor, a thermocouple), a temperature of at least one of a contact surface of the stimulation device and patient tissue adjacent to the contact surface during delivery of the electrical stimulation, the temperature sensor providing thermal feedback regarding the measured temperature to the stimulation device; activating a cooling mechanism to cool the contact surface of the stimulation device; contact of the stimulation device in response to thermal feedback received from the temperature sensor, cooling the contact surface to prevent damage to the patient's tissue when electrical stimulation is delivered by keeping the patient's tissue temperatures below a tissue-destructive temperature, and activating a cooling mechanism to maintain the temperature of the contact surface of the stimulation device below the tissue-destructive temperature in response to thermal feedback regarding the measured temperature received from the temperature sensor.

[0093] According to another aspect, the invention relates to a non-transitory computer-readable medium. The computer-readable medium having instructions stored thereon, wherein execution of the instructions by a processor causes the processor to perform any of the methods recited above.

[0094] Details of one or more embodiments of the invention are set forth in the accompanying drawings and the description below. Other features, objects and advantages of the invention will be apparent from the description and drawings, and from the claims. Brief description of the drawings

[0095] The patent or application file contains at least one color drawing. Copies of such patent or patent application publication with color drawings will be provided by the office upon request and payment of the necessary fee.

[0096] [Fig.l] is a schematic representation of an exemplary electrical stimulation device.

[0097] [Fig.2A] is a schematic representation of the electrical stimulation device of [Fig.l].

[0098] [Fig.2B] is a schematic representation of the electrical stimulation device of [Fig.l].

[0099] Figures 3A to 3G are schematic representations of examples of percutaneous electrodes.

[0100] Figure 4A is a schematic representation of an exemplary percutaneous electrode positioned adjacent to a target nerve.

[0101] Figure 4B is a schematic sectional view of the exemplary electrode of Figure 4A.

[0102] [Fig.5] shows various examples of bipolar electrical contact and electrode configurations.

[0103] Figures 6A and 6B are an example of an electrode connection.

[0104] [Fig.7A] is an example of electrical stimulation, and control parameters corresponding, which can be applied to nervous tissue and / or neighboring tissues to selectively and / or reversibly inhibit the activities of the nervous system.

[0105] Figures 7B, 7C, 7D, 7E, 7F, 7G, 7H, 7I, 7J, 7K, 7L, 7M, 7N, 7O and 7P each show a waveform for electrical stimulation.

[0106] [Fig.8] is a schematic representation of the positioning of an electrode percutaneously and the delivery of electrical stimulation to a target nerve structure.

[0107] Figures 9A and 9B are schematic representations of electrode positioning and delivery of electrical stimulation to the sphenopalatine ganglion.

[0108] [Fig. 10] is a table proving the experimental results.

[0109] [Fig. 11] is a table proving the experimental results.

[0110] The same reference symbols in the different drawings indicate the same elements. DEFINITIONS

[0111] The following description of certain examples of the inventive concepts should not be used to limit the scope of the claims. Other examples, features, aspects, embodiments and advantages will become apparent to those skilled in the art from the following description. As will be understood, the device and / or methods are capable of comprising other obvious and different aspects, all without departing from the spirit of the inventive concepts. Accordingly, the drawings and description should be considered illustrative and not restrictive in nature.

[0112] For the purposes of this disclosure, certain aspects, advantages, and novel features of the embodiments of the present disclosure are described herein. The methods, systems, and apparatuses described are not to be construed as limiting in any way. Rather, this disclosure relates to all novel and non-obvious features and aspects of the various embodiments described, alone and in various combinations and subcombinations with each other. The methods, systems, and apparatuses described are not limited to any specific aspect, any specific feature, or combination thereof, nor do the methods, systems, and apparatuses described require that any one or more specific advantages be present or problems be solved.

[0113] Features, integers, characteristics, compounds, chemical moieties or groups described in conjunction with a particular aspect, embodiment or example of the invention should be understood as being applicable to any other aspect, embodiment or example described herein, unless inconsistent therewith. All features disclosed in this specification (including the claims, the accompanying abstract and drawings) and / or any steps of any method or process so disclosed may be combined in any combination, except for combinations where at least some of these features and / or steps are mutually exclusive. The invention is not limited to the details of the preceding embodiments. The invention applies to any new feature or combination of features described in this specification (including the claims, the accompanying abstract and drawings), to any new step or combination of steps of any method or process so disclosed.

[0114] Ranges may be expressed herein as "about" a particular value and / or to "about" another particular value. When such a range is expressed, another aspect comprises from a particular value and / or to another particular value. Similarly, when values ​​are expressed as approximations, using the antecedent "about", it will be understood that the particular value forms another aspect. It will be further understood that the endpoints of each of the ranges are meaningful both relative to the other endpoint and independently of the other endpoint.

[0115] The terms "possible" and "possibly" as used herein mean that the event or circumstance described herein may or may not occur and that the description includes instances where said event or circumstance occurs and instances where it does not.

[0116] The terms "proximal" and "distal" are used herein as relative terms that refer to regions of a nerve, positions of nerves, or regions of a stimulation device. "Proximal" means a position closer to the spinal cord, brain, or central nervous system, while "distal" indicates a position farther from the spinal cord, brain, or central nervous system. When referring to the position on a neural structure in the peripheral nervous system or along an appendage, proximal and distal refer to positions either closer to the central nervous system or farther from the central nervous system along the pathway followed by that neural structure or appendage.When referring to the position on a neural structure in the spinal cord, proximal and distal refer to positions either closer to the brain or further from the brain along the pathway followed by the neural structure.

[0117] Throughout the description and claims of the invention, the word "include" and variations of the word, such as "comprising" and "comprises", mean "including, but not limited to" and are not intended to exclude, for example, other additives, components, integers or steps. The terms "example" and "for example" mean "an example of" and are not intended to give an indication of a preferred or ideal aspect. The term "such as" is not used in a restrictive sense, but for explanatory purposes.

[0118] As used herein, the term "nervous structure" or "neural structure" refers to a structure comprising nervous and non-nervous tissue. In addition to nervous tissue (such as neurons and components of neurons, including axons, cell bodies, dendrites, and synapses of neurons), nervous structures may also include non-nervous tissue such as glial cells, Schwann cells, myelin, immune cells, connective tissue, epithelial cells, neuroglial cells, astrocytes, microglial cells, ependymal cells, oligodendrocytes, satellite cells, cardiovascular cells, blood cells, etc.

[0119] As used herein, the term "stimulating electrode", also referred to as "cathode" in the case of unipolar stimulation, refers to an electrode responsible for delivering therapeutic energy to the nerve. In the case of bipolar or multipolar stimulation, all electrical contacts are considered to be stimulating electrodes.

[0120] As used herein, the term "return electrode," also referred to as "anode" in the case of unipolar stimulation, refers to an electrode responsible for providing a return path for current flowing through the body. For example, the return electrode provides a return path for current being delivered to the target neural structure via the stimulating electrode.

[0121] As used herein, the terms "electrical signal", "electrical stimulation", "electrical stimulation signal", and "stimulation wave" refer to the electrical signal delivered by the controller to the tissue by means of the stimulating electrodes or, in the case of unipolar stimulation, by means of the stimulating electrode and the return electrode. For example, the electrical signal may be described as a time-varying voltage, current, power, or other electrical measurement. The delivery of the electrical signal to the target tissue is referred to as electrical treatment, electrical therapy, or simply treatment or therapy. The electrical signal creates an electric field in the tissue, so that control of the electrical signal strongly influences control of the electric field in the tissue.

[0122] As used herein, the term "treatment site" refers to the site of the neural and non-neural structure to which the electrical signal is delivered by means of the electrode(s).

[0123] As used herein, the term "modulate" means a modification or change in the transmission of information. For example, this includes both excitation, stimulation, and inhibition / interruption of the passage of impulses along the axon of the neuron in a nerve. Modulation of nerve fiber activity includes the inhibition of nerve signal transmission to the point of creating a blocking effect, including a partial or complete blocking effect. Modulation of nerve activity also includes altering the trafficking of molecules such as macromolecules along the nerve fiber. Modulation of nerve activity also includes changing the function downstream of the neuron (e.g., at cell bodies and synapses), altering signaling so as to alter signaling in other neurons (e.g., neurons in the central nervous system such as the spinal cord or brain), altering the function of non-nervous tissue within the neural structure, or otherwise altering processes, function, or activity in the target nervous or non-nervous tissue.

[0124] As used herein, the terms "inhibit" and "attenuate" refer to any rate of reduction, including partial or complete reduction of nerve signal activity through a nerve structure, e.g., reducing the passage of impulses along the neuron's axon in a nerve.

[0125] As used herein, the term "percutaneous" refers to electrical stimulation applied using one or more electrodes penetrating through the surface of the skin so that an electrode delivering electrical stimulation to a target nerve located beneath the skin is also located beneath the skin. For percutaneous electrical stimulation, it is contemplated that return electrodes or anodes may be located beneath the skin or at the surface of the skin. The term "percutaneous electrode" refers to electrode arrays inserted through the skin and directed proximal to the nerve (distance mm to cm) in a minimally invasive manner to electrically affect the physiology of the neural structure.

[0126] As used herein, the terms "pain sensation" and "painful sensation" refer to an unpleasant sensation generated, for example, by the activation of sensory nociceptors. Nociception describes the perception of acute pain and is generally caused by the activation of sensory nociceptors or by the disruption of nociceptor pathways (e.g., severed neurons or disrupted nociceptors). Chronic pain sensation may also be generated by the activation of nerve fibers, resulting in an unpleasant perception similar in nature to that generated by the activation of nociceptors (e.g., neuropathic pain). In some cases, for example, after surgery to treat chronic pain, acute pain sensation and chronic pain sensation may contribute in a mixed manner to the overall pain sensation.

[0127] As used herein, the term "target nerve" is synonymous with "neural structure" or "nerve structure" and refers, for example, to mixed nerves containing fibers motor nerves and sensory nerve fibers. They can also be sensory nerves containing only sensory nerve fibers and / or motor nerves containing only motor nerve fibers.

[0128] As used herein, the term "transmucosal" refers to electrical stimulation applied to the mucosal tissue covering a targeted nerve structure using one or more electrodes. The electrical stimulation passes through the mucosal tissue to the targeted nerve structure.

[0129] As used herein, the terms "preserve" and "preservation" refer to cases in which nerve function is partially but not completely maintained, as well as cases in which a function is completely maintained. In comparative cases, one function may be inhibited while another is preserved, suggesting that, comparatively, the inhibited function has suffered a greater reduction than the preserved function. Specifically, in comparative cases, inhibition of one function and preservation of another function does not require complete preservation or complete inhibition of either function. DETAILED DESCRIPTION

[0130] ANATOMY AND PHYSIOLOGY

[0131] As described above and as will be explained in more detail below, the present invention relates to a device and method for selectively and reversibly modulating targeted nervous or non-nervous tissue of a nervous structure by the application of an electrical signal to inhibit pain while preserving other sensory and motor functions, as well as proprioception.The device and method can be used to treat acute pain (such as surgical pain, post-operative pain, painful trauma), neuropathic pain, chronic pain, and head and facial pain (such as migraine, cluster headache, occipital neuralgia, tension headache, sinus headache, cervicogenic headache, postherpetic neuralgia, post-traumatic pain, chronic daily headache (transformed migraine) via applying an electrical signal to a target nervous or non-nervous tissue of a nervous structure to modulate or inhibit nerve signaling.

[0132] Pain is a noxious perception generated in the conscious mind. In healthy humans, the perception of pain is generated by the activation of sensory nociceptors and the subsequent transmission of noxious signals to the brain through one or more neural pathways. Pain can be created by the activation of a neural pathway, at any point along that neural pathway, resulting in the perception of pain. In healthy humans, pain-generating neural pathways are typically activated via sensory nociceptors, which are sensory nerve endings tuned to detect and signal noxious events (e.g., harmful mechanical or thermal tissue injury). This type of pain typically represents an actual noxious pathology, and this type of pain resolves when the noxious pathology resolves. In cases where the noxious event is not chronic tissue dysfunction, this type of pain is referred to as acute pain. In contrast, chronic pain represents pathologies in which pain-generating neural pathways are persistently modulated due to chronic tissue dysfunction or nerve dysfunction.This may be due to actual activation of sensory nociceptors at a chronically dysfunctional tissue site or to dysfunction of the nervous tissue or tissue supporting the nervous tissue that results in modulation at any point along the pain-generating neural pathways.

[0133] Interventions to treat pain may be designed to directly or indirectly modulate nerve signal transmission via pain-generating neural pathways at any level of those pathways. For example, direct blockade of axonal conduction in nerve fibers attached to sensory nociceptors may block pain perception. As a further example, indirect modulation of synaptic transmission in the spinal cord or nerve ganglia may be achieved by activating or blocking other inputs to the spinal cord or ganglia and may result in modulation along a pain-generating neural pathway.As another example, inhibition of parasympathetic outflow in the sphenopalatine ganglion may indirectly influence head and facial pain, such as migraine, by modulating sensory inputs to the brain (e.g., via the superior salivatory nucleus). Thus, it is desirable to target various neural structures when modulating and treating acute and chronic pain.

[0134] Targeted nerve structures include peripheral nerves (small diameter and large diameter), cranial nerves, ganglia, autonomic nerves, plexuses, and the spinal cord. Ganglia include at least one of dorsal root ganglia, sympathetic ganglia, parasympathetic ganglia, a sphenopalatine ganglion, a gasserian ganglion, and autonomic ganglia in general. Generally, large peripheral nerves are peripheral nerves having a diameter greater than about 2.5 mm. Large peripheral nerves include, for example, the femoral nerve, sciatic nerve, vagus nerve, tibial nerve, peroneal nerve, median nerve, radial nerve, and ulnar nerve. Small peripheral nerves include, for example, the saphenous nerve, sural nerve, genicular nerves, nerves cranial nerves (such as the trigeminal nerve and the occipital nerve), the obturator nerve, and distal portions of larger nerves (such as the distal portions of the vagus, peroneal, median, radial, and ulnar nerves). Targeted ganglia may include dorsal root ganglia, sympathetic ganglia, parasympathetic ganglia, a sphenopalatine ganglion (SPG), a gasserian ganglion, plexuses, and the spinal cord. Each of these nervous structures includes nervous tissue as well as non-nervous tissue that supports the nervous tissue and can influence the transmission of information along pain-generating neural pathways.An example of non-nervous tissue may include, for example, glial cells, Schwann cells, myelin, immune cells, connective tissue, epithelial cells, neuroglial cells, astrocytes, microglial cells, ependymal cells, oligodendrocytes, satellite cells, cardiovascular cells, blood cells, etc. Nervous tissue generally refers to neurons including components such as axons, cell bodies, dendrites, receptor terminals, receptors, and synapses.

[0135] Importantly, in the context of the present invention, modulation of nervous tissue (neurons including components such as axons, cell bodies, dendrites, receptor terminals, receptors and synapses) and / or non-nervous tissue (such as glial cells, Schwann cells, myelin, immune cells, connective tissue, epithelial cells, neuroglial cells, astrocytes, microglial cells, ependymal cells, oligodendrocytes, satellite cells, cardiovascular cells, blood cells, etc.) may be responsible in part or in whole for the therapeutic inhibition of pain.

[0136] Peripheral nerves are primarily composed of axons, whereas other neural structures, such as ganglia and the spinal cord, comprise many components, including axons, cell bodies, dendrites, and synapses. Within a nerve structure, there is variability in the nature of these components, including variability in size, shape, and interface with non-nervous supporting tissue. For example, peripheral nerves often contain both large and small diameter axons. Schwann cells are non-nervous supporting cells that surround some axons and comprise an insulating envelope rich in layers of lipid bilayers called a myelin sheath. Some axons are surrounded by a myelin sheath, and some axons are not surrounded by a myelin sheath. Generally, the structure of different nerve components is related to their function.For example, large diameter axons generally transmit nerve signals faster than small diameter axons due to the relatively large increase in axial conductance. compared to a modest increase in membrane conductance as a function of diameter. Similarly, the presence of a myelin sheath on large-diameter axons further increases action potential conduction velocity by increasing resistance to transmembrane current flow between unmyelinated areas of the axon, called nodes of Ranvier. Nodes of Ranvier are brief unmyelinated portions of fibers. Action potentials are relayed along the axon by a burst of transmembrane current flow at each subsequent node of Ranvier.Peripheral nerve axons that typically transmit information from the periphery to the central nervous system (e.g., sensory information, including pain) are often called afferent fibers, while axons that typically transmit information from the central nervous system to the periphery (e.g., motor information) are often called efferent fibers.

[0137] As used herein, the term "A fiber" refers to the myelinated peripheral afferent or efferent axons of the somatic nervous system. Generally, A fibers are associated with proprioception, somatic motor skills, sensations of touch and pressure, as well as sensations of pain and temperature. A fibers typically range in diameter from about 1 to 22 micrometers (pm) and have conduction velocities ranging from about 2 meters per second (m / s) to over 100 m / s. Each A fiber has dedicated Schwann cells forming the myelin sheath around the fiber. As described above, the myelin sheath has a high lipid content, increasing the electrical resistance to transmembrane current flow and contributing to the high conduction velocity of action potentials along the nerve fiber. A fibers include alpha, beta, delta, and gamma fibers.Alpha, beta, and gamma A fibers have diameters between 5 and 20 micrometers (pm) and are associated with motor function, low-threshold sensory function, and proprioception, but not pain. Delta A fibers are associated with pain and have smaller diameters in the range of 1 micrometer to 5 micrometers (pm).

[0138] As used herein, the term "C fiber" refers to unmyelinated peripheral axons of the somatic nervous system having conduction velocities less than about 2 m / s. C fibers are about 0.2 to 1.5 micrometers (pm) in diameter and include dorsal root and sympathetic fibers. They are primarily associated with sensations such as pain and temperature, some mechanoreception, reflex responses, autonomic effector activity, and visceral function.

[0139] In a peripheral nerve, the sensation of pain perceived as dull and persistent is often called "slow pain" and is transmitted in the peri-nerves pherical by C fibers that transmit nerve signals relatively slowly. The sensation of pain perceived as sharp and rapid is often referred to as "fast pain" and is transmitted in peripheral nerves by A6 fibers that have a higher conduction velocity than C fibers. A6 fibers generally comprise small-diameter sensory axons that are lightly myelinated compared to unmyelinated C fibers. Acute and chronic pain can involve both A6 and C fibers.

[0140] In addition to the examples given above for peripheral nerve axons, similar principles of structure and function for components of neural structures, such as axons, cell bodies, dendrites, receptor terminals, receptors, and synapses, apply to various neural structures, including a peripheral nerve, a cranial nerve, a ganglion and an autonomic nerve, a plexus, and the spinal cord. Subcellular structures within components of non-nervous and nervous tissues, such as cell membranes, lipid bilayers, ion channels, mitochondria, microtubules, the nucleus, vacuoles, and other components of the cytoplasm, are also related to the function of these components of neural structures.Additionally, downstream structures (e.g., cellular and subcellular structures downstream of the treatment site) may also be functionally or structurally impacted primarily or secondary to neural treatments (e.g., downstream modulation of gene transcription, synaptic transmission, epigenetics, or modulation along multiple molecular signaling cascades within a neuron). The downstream molecular and cellular machinery, and even the connectivity and communication between cells, may be very different for pain pathways compared to motor, non-pain sensory, and proprioceptive pathways.

[0141] As a further example, the sphenopalatine ganglion consists of parasympathetic neurons, sympathetic neurons, and sensory neurons. In the sympathetic ganglion, cell bodies and synapses are present for parasympathetic neurons, but not for sympathetic or sensory neurons. Rather, only axons of sympathetic and sensory neurons pass through the sphenopalatine ganglion. The device and method of the present invention can be used to selectively and / or reversibly modulate nerve signal transmission in one of the types of neural structure (e.g., cell bodies, synapses, axons) without modulating other neural structures present in the ganglion.For example, modulation or inhibition of transmission via the parasympathetic neuronal pathway, e.g., by inhibiting signal transmission via cell bodies or synapses in the sphenopalatine ganglion, can be achieved while preserving signaling via sympathetic pathways and at least . some of the sensory pathways. As a further example, modulation or inhibition of transmission via small-diameter sensory neurons can be achieved while preserving signaling via sympathetic, parasympathetic, and other sensory fiber pathways. As a further example, modulation of the parasympathetic pathway and the small-diameter sensory pathway can be achieved while preserving signaling via all other pathways in the ganglion. Notably, each type of nervous component in a neural structure may have its own non-nervous supporting tissue, contributing to the ability to selectively target modulation via specific pathways.

[0142] As will be described in more detail below, the device and method of the present invention can be used to selectively and reversibly modulate nerve signal transmission, for example by inhibiting or blocking nerve signal transmission, to inhibit pain. This selective and reversible inhibition of pain does not present a risk of neuronal toxicity, vascular toxicity, or injectable chemical allergy.The device of the present invention is non-destructive to the target nerve structure and is suitable for treating chronic pain indications without the risks of atrophy, neuropathy and pain, and is well suited for acute pain indications where one or more nerves are treated before, during or shortly after surgery, so that the patient can go home without a device while still enjoying pain relief for a day or several weeks after surgery, for example after a joint replacement or other orthopedic procedure. In other words, a device in which long-term direct contact with the target area or nerve to be treated (for example via an implantable generator and nerve sleeve) is not required.However, if desired and particularly for chronic pain indications, the device can still be implanted or partially implanted and / or taken home with the patient.

[0143] EXAMPLE OF DEVICE

[0144] [Fig.l] provides a schematic representation of an exemplary electrical stimulation device 100. The electrical stimulation device 100 may be used to selectively and reversibly modulate targeted nervous or non-nervous tissue of a nervous structure with the application of an electrical signal to treat a pathological condition of a patient. The stimulation device 100 includes an electrode 120 that delivers electrical stimulation at the treatment site, e.g., that delivers the electrical stimulation to the targeted nervous or non-nervous tissue of the nervous structure. The electrical stimulation may be delivered by a percutaneously placed lead (L) and electrode 120, by an implanted lead (L) and electrode 120, or by an electrode 120 advanced through a body opening and positioned adjacent to (e.g., near or in contact with) the mucosal tissue covering the targeted nerve structure (e.g., sphenopalatine ganglion, gasserian ganglion). An example wherein the mucosal tissues include oral mucosa, nasal oral mucosa, gastrointestinal (GI) tract mucosa, bowel mucosa, bladder mucosa. Electrode 120 generates an electric field at the treatment site that results in selective and reversible modulation of nerve fiber activity to inhibit pain. As noted above, “modulation” of nerve fiber activity includes both excitation and inhibition / interruption of impulse passage along the neuron’s axon in a nerve and may include inhibition of nerve signal transmission to the point of creating a blocking effect.

[0145] The delivery of the electrical stimulation signal includes interactions with other nearby tissues. For example, in the case of percutaneous application and electrode positioning, the electrical signal stimulation is delivered via the electrode 120 which has passed through and traveled through the patient's external tissues, including their skin, fat, bones, and muscles, in order to place the electrode 120 in proximity to a target neural structure. In this example, the electrical stimulation influences not only the target neural structure, but also surrounding tissues such as connective tissue, nerve structure-supporting tissues, adipose, bone, muscle, and cardiovascular tissues such as those present in and around blood vessels. In the case of transmucosal application, the electrical signal stimulation is delivered via the electrode 120 which is placed in proximity (e.g., near or in contact with) the overlying mucosal tissue.Electrical stimulation may affect the targeted nerve structure, as well as tissues below and around the electrode 120, tissues interposed between the electrode 120 and the target nerve structure, and other surrounding tissues (including skin, fat, muscle, bone, cartilage, connective tissue, nerve structure support tissues, cardiovascular tissues and cells such as those in and around blood vessels, and other tissues in the epidermis, dermis, as well as nerve receptors, hair follicles, sweat glands, sebaceous glands, apocrine glands, and lymphatic vessels).While the application of electrical stimulation at the treatment site, in both percutaneous and transnasal applications, will modulate (e.g., selectively and / or reversibly) the targeted nervous or non-nervous tissue of the nervous system structure to inhibit pain perception, the electrical stimulation and pacing device 100 is designed to cause no damage to the nervous system structure and / or surrounding tissue (e.g., overlying mucosal tissue).

[0146] As schematically illustrated in [Fig.l], the stimulation device 100 and The electrode 120 / L-leads may be reused or disposable. Desirably, the nerve structure may be modulated via a disposable L-lead and electrode 120, and driven by a reusable external stimulator / signal generator 140 and controller 130. It is contemplated that the stimulation device 100, as a whole, may be sized and configured for implantation into the patient (beneath the patient's skin) at a location adjacent to the targeted nerve structure (N), shown schematically in [Fig. 2A]. The power source 180, providing electrical power to the controller 130 / signal generator 140, may be positioned inside or outside the patient.It is also contemplated that only the leads / electrode 120 are implanted in the patient and the remaining components, including the signal generator 140 and the controller 130, are incorporated into a handheld device that can be easily manipulated to deliver the therapy, shown schematically in [Fig. 2B]. It is further contemplated that the stimulation device 100, including the signal generator 140, the controller 130 and the leads / electrode 120 may be incorporated into a larger, non-handheld device designed to remain on a fixed surface or on a cart that can be moved around the premises of a medical clinic, with only the electrodes 120 / leads (L) being advanced percutaneously through an opening in the patient's skin or through another opening in the patient's body (e.g., through the nasal cavity).

[0147] The stimulation device 100 may be used to reversibly and / or selectively inhibit pain while preserving another sensory function. Specifically, the electrical stimulation provided by the stimulation device 100 may reversibly and / or selectively modulate nerve signal transmissions by nerve fibers that are responsible for pain transmission while preserving nerve signal transmission by nerve fibers responsible for other sensory and motor functions, and proprioception.

[0148] With respect to reversibility of the modulated nerve function, the stimulation device 100 may reversibly inhibit pain, for example, by inhibiting or blocking nerve signal transmission for a period of about 1 day to about 30 days. Preferably, pain perception is inhibited for a period of about 5 days to about 30 days. For chronic pain, pain perception is inhibited for a period of about 90 days to about 356 days. Reversibility of nerve signal transmission and subsequent recovery of function after the appropriate time period after treatment is important, particularly for acute post-surgical pain. The parameters of the stimulation waveform may be adjusted to adjust the expected duration of pain inhibition and to ensure that pain inhibition does not last longer than desired. For example, in patients undergoing knee replacement, it is important that pain perception returns 15 to 30 days after surgery, as acute pain sensations are an important protective signal to help patients regulate their physical activity during recovery.

[0149] With respect to the selectively modulated nerve function, the stimulation device 100 may selectively modulate nervous or non-nervous tissue inhibiting pain perception and preserving other sensory and motor functions, as well as proprioception. This produces a scenario in which the electrical neuromodulation treatment is selective for a subset of nerve structure functions while preserving other nerve structure functions. Pain perception is inhibited, while other sensory and motor functions and proprioception are preserved. For example, the electrical signal disrupts the transmission of pain signals from the periphery to the brain by inhibiting nerve signal transmission through the nerve fibers responsible for pain transmission.This includes direct inhibition of pain signal transmission in neurons of the target neural structure or can be achieved by indirect inhibition of other downstream neurons responsible for transmitting pain signals to the brain, such as neurons in the central nervous system (e.g., spinal cord and brain).

[0150] Preserved sensory function includes, for example, non-painful tactile sensation (low threshold sensory function), vision, hearing, taste, smell, and balance. It is also contemplated that the described electrical signal may modulate nerve signal transmission by nerve fibers responsible for transmitting thermoreception, autonomic activity, and visceral function.

[0151] Selective modulation of pain perception is particularly useful in cases where modulation must be applied to mixed nerve structures, such as peripheral nerves containing motor and sensory axons. For example, in many surgical procedures, it is desirable to modulate pain transmitted via mixed nerves to treat acute surgical pain, while preserving motor, sensory, and proprioceptive function of the nerve. Preserving motor, sensory, and proprioceptive function during pain treatment is particularly important in cases where physical therapy or other movement of an appendage must be performed during recovery from surgery. For example, many post-surgical care programs include steps to help patients avoid muscle atrophy or other functional stagnation after surgery.Preserving control of motor, sensory, and proprioceptive functions while treating pain may enable and enhance such programs.

[0152] As described in more detail below, one or more parameters of the electrical stimulation may be adjusted to selectively block transmission of the nerve signal through a selected type of nerve fiber and / or through a selected region of the nerve structure.The adjustable parameters of the electrical stimulation include, for example, a waveform, a wave frequency, a wave amplitude, an electric field strength generated at the electrode 120 (e.g., measured at the electrode or the treatment site), a continuous wave offset, a wave duty cycle (e.g., continuous delivery and / or intermittent delivery via the electrode), a tissue temperature, a parameter of the cooling mechanism (e.g., a cooling rate, a coolant flow rate, a coolant pressure, a temperature measured at the treatment site or a portion of the cooling mechanism), and a treatment duration.These parameters are adjustable and controllable by means of the controller 130, the user interface 170 and a cooling mechanism which may be incorporated into the stimulation device 100, as described in more detail below.

[0153] For example, when the targeted nerve structure is a peripheral nerve, e.g., a large peripheral nerve such as those having a diameter greater than about 2.5 mm, the electrical stimulation may inhibit nerve signal transmission through myelinated Aδ fibers and / or unmyelinated C fibers in the peripheral nerve, wherein the electrical stimulation preserves nerve signal transmission through at least one of the Aδ and Aδ fibers, and / or motor fibers. It is contemplated that at least one parameter of the electrical stimulation may be adjusted to selectively inhibit myelinated Aδ fibers and / or unmyelinated C fibers, while preserving nerve signal transmission through at least one of the Aδ and Aδ fibers, and / or motor fibers.

[0154] In another example, the electrical stimulation may inhibit nerve signal transmission through myelinated Aδ fibers and / or unmyelinated C fibers in the target peripheral nerve, wherein the electrical stimulation preserves nerve signal transmission through at least one of the Aδ and Aα fibers, and / or motor fibers in a neighboring nerve or nerve fascicle. By selectively blocking pain sensation while allowing nerve signal transmission through selected nerve fibers of neighboring nerves and / or nerve fascicles, the vividness of the pain sensation may be reduced, thereby preventing other large motor fibers from being affected.

[0155] In another example, the targeted nerve structure covered by a layer of mucosal tissue, e.g., the Gasserian ganglion, the sphenopalatine ganglion (SPG). Electrical stimulation can be delivered through the mucosal tissue to modulate the single nerve transmission by a particular nerve fiber type of the underlying nerve structure and adjacent non-nervous tissue. Nerve fiber types include, for example, parasympathetic nerve fibers, sympathetic nerve fibers, sensory nerve fibers). For example, when the targeted nerve structure includes the sphenopalatine ganglion (SPG), electrical stimulation selectively inhibits nerve signal transmission through the parasympathetic nerve fibers comprising the SPG, the sympathetic nerve fibers comprising the SPG, and / or the sensory nerve fibers comprising the SPG. It is contemplated that this nerve signal transmission may be inhibited while also selectively preserving the function of at least one of the non-selected nerve fiber types (e.g., parasympathetic, sympathetic, and sensory nerve fibers comprising the SPG).

[0156] It is further contemplated that at least one parameter of the electrical stimulation may be adjusted to differentially inhibit the function of myelinated Aδ fibers such that myelinated Aδ fibers have a higher percentage of inhibited fibers than unmyelinated C fibers. Nerve signal transmission via myelinated Aδ fibers is generally associated with the sensation of fast, sharp / shooting pain, whereas nerve signal transmission via unmyelinated C fibers is generally associated with the sensation of dull / acute pain. Accordingly, the electrical stimulation may be adjusted to differentially inhibit the function of nerve fibers responsible for the sensation of sharp pain, such that these fibers have a higher percentage of inhibited fibers than nerve fibers responsible for the sensation of dull / acute pain.

[0157] Similarly, it is further contemplated that at least one parameter of the electrical stimulation may be adjusted to differentially inhibit the function of unmyelinated C-fibers, such that unmyelinated C-fibers have a higher percentage of inhibited fibers than myelinated A-fibers. That is, the electrical stimulation may be adjusted to differentially inhibit the function of nerve fibers responsible for a dull / hyperacute pain sensation, such that these fibers have a higher percentage of inhibited fibers than nerve fibers responsible for a fast, sharp, and stabbing pain sensation.

[0158] In another example, where the targeted nerve structure is covered by a layer of mucosal tissue, such as the Gasserian ganglion or the sphenopalatine ganglion (SPG), the electrical stimulation can be adjusted to differentially inhibit the function of the parasympathetic, sympathetic, and / or sensory nerve fibers of the ganglion. For example, the electrical stimulation delivered to the target site can differentially inhibit the function of the parasympathetic nerve fibers of the SPG, with the parasympathetic nerve fibers having a higher percentage of inhibited fibers. important than non-parasympathetic nerve fibers and non-nervous tissue. Similarly, electrical stimulation delivered to the target site can differentially inhibit the function of sympathetic nerve fibers in the SPG, with sympathetic nerve fibers having a greater percentage of inhibited fibers than non-sympathetic fibers and non-nervous tissue. Similarly, electrical stimulation delivered to the treatment site can differentially inhibit the function of sensory nerve fibers in the SPG, with sensory nerve fibers having a greater percentage of inhibited fibers than parasympathetic, sympathetic, and non-nervous tissue fibers.

[0159] An additional mechanism of inhibition of pain perception is when the inhibitory effect is downstream or secondary to the treatment site. For example, when the targeted nerve structure is a large peripheral nerve, e.g., a nerve with a diameter greater than about 2.5 mm, electrical stimulation may modulate the activity or function of nervous or non-nervous tissues, resulting in the activation of a biochemical signaling cascade that causes a decrease in the activation of spinal or cortical neurons representing pain (e.g., via modulation of synaptic signaling), while nerve signal transmission by neurons in the central nervous system and peripheral nervous system is involved in the detection, transmission, processing, and generation of non-painful touch, motor control, and proprioception are preserved.It is envisaged in this case that at least one parameter of the electrical stimulation can be adjusted to selectively inhibit downstream or secondary effects of pain originating from Aô fibres and / or originating from unmyelinated C fibres, while the function of neurons in the central nervous system and peripheral nervous system involved in the detection, transmission, processing and generation of non-painful touch, motor control and proprioception are preserved.

[0160] It is further contemplated in this case that at least one parameter of the electrical stimulation may be adjusted to differentially inhibit downstream or secondary effects of pain from myelinated Aδ fibers, such that the downstream or secondary effects of the myelinated Aδ fibers are inhibited more than the downstream or secondary effects of the unmyelinated C fibers. Similarly, it is further contemplated in this case that at least one parameter of the electrical stimulation may be adjusted to differentially inhibit downstream or secondary effects of pain from unmyelinated C fibers, such that the downstream or secondary effects of the unmyelinated C fibers are inhibited more than the downstream or secondary effects of the myelinated Aδ fibers.

[0161] EXAMPLE OF ELECTRICAL STIMULATION

[0162] As described above, the electrode 120 provides an electrical signal at the treatment site to selectively modulate nervous or non-nervous tissue by inhibiting pain perception and preserving other sensory and motor functions, as well as proprioception. The electrical signal disrupts the transmission of pain signals by modulating nervous or non-nervous tissue.Various parameters of the electrical signal may be adjusted, as set forth below, to modulate function via the nerve structure, including, for example, a stimulation pulsed waveform (also referred to herein as a "waveform"), a stimulation pulsed frequency (also referred to herein simply as "frequency"), a stimulation pulsed amplitude (also referred to simply as "amplitude"), an electric field strength generated at the electrode 120, a DC wave offset, a wave duty cycle (e.g., continuous delivery and / or intermittent delivery via the electrode), a tissue temperature, a cooling mechanism parameter, and a treatment duration.It is contemplated that some parameters may be adjusted individually to produce a desired effect, while others are adjusted in combination with some interdependence on each parameter adjustment within an effect to produce the desired effect. As described above and in more detail below, various parameters and / or combinations of parameters of the electrical signal are adjusted to selectively and reversibly modulate nerve signal transmission through a selected type of nerve fiber and / or through a selected region of the nerve structure.

[0163] To facilitate selective and / or reversible inhibition of nervous system activities (e.g., to block acute pain), the device and stimulation system are configured, in some embodiments, to apply high-frequency stimulation directly to the nerve and / or surrounding tissue to invoke a sufficient pain-inhibiting response by the nervous system. The high-frequency stimulation may be applied in pulses during a single treatment / application and in a manner that does not damage the surrounding tissue and the nervous tissue.It has been observed that high-frequency stimulation applied at 500 kHz in a series of 20 millisecond pulses up to 100 V for a few minutes (and up to a temperature of 42 ^C) can be applied to invoke a sufficient pain inhibition response that can selectively disrupt acute pain sensation but not affect other neurological functions such as motor control. It has also been observed that the same high-frequency stimulation can be applied to invoke a reversible pain inhibition response as long as pain is blocked for a clinically relevant duration that can last from 1 to 30 days. Without wishing to be bound by any particular theory, it is hypothesized that the selective and reversible effect may . be attributed to the particularly high voltage field that is applied to the tissue without causing thermal damage to the treatment site, especially at the nerve level.

[0164] [Fig.7A] shows an example of electrical stimulation and corresponding control parameters, which may be applied to the nerve and / or neighboring tissue to selectively and / or reversibly inhibit nervous system activities, according to an illustrative embodiment. As shown in [Fig.7A], the electrical stimulation may be defined by control parameters such as amplitude, pulse duty cycle (e.g., including a pulse envelope duration and an inter-envelope interval), stimulation waveform, and signal frequency. In addition to a stimulation frequency of 500 kHz, other stimulation frequency ranges may be applied.In some embodiments, the stimulation device and system are configured to apply electrical stimulation having a stimulation frequency selected from the group consisting of about 100 kHz, about 150 kHz, about 200 kHz, about 250 kHz, about 300 kHz, about 350 kHz, about 400 kHz, about 450 kHz, about 500 kHz, about 550 kHz, about 600 kHz, about 650 kHz, about 700 kHz, about 800 kHz, about 850 kHz, about 900 kHz, about 950 kHz, and about 1 MHz. Applying electrical stimulation having a pulse duty cycle may allow for a higher current amplitude or voltage and / or a higher frequency (to generate a higher voltage field at the treatment site) without causing thermal damage to the tissue.The application of electrical stimulation having a non-sinusoidal waveform can be used to adjust the energy density applied in a given electrical stimulation and / or to also allow the application of a higher electric field.

[0165] Figures 7B, 7C, 7D, 7E, 7F, 7G, 7H, 7I, 7J, 7K, 7L, 7M, 7N, 7O, and 7P each show a waveform for electrical stimulation, in accordance with an illustrative embodiment. As shown in Figures 7B-7F, in some embodiments, the stimulation waveform is a sine waveform (Figures 7B, 7G), a triangle waveform (Figure 7C), a square or rectangular waveform (Figure 7D), a sawtooth triangle waveform (Figure 7E), or a complex waveform (Figure 7F).

[0166] In some embodiments, the frequency of a given pulse is modified (e.g., as a chirp, as shown in Figures 7K, 7L, and 7M). In some embodiments, the amplitude envelope of the electrical stimulation is modified for a given pulse (Figures 7K and 7L).

[0167] In some embodiments, the electrical stimulation is a controlled output. by voltage. In some embodiments, the electrical stimulation is a current-controlled output. In some embodiments, the electrical stimulation is a power-controlled output.

[0168] In some embodiments, the stimulation waveform comprises a continuous charge-balanced sinusoid (see, for example, Figures 7B-7F, 7K, 7L, 7M, 7N, and 7P), or an additive combination of sinusoids (for example, as a sinusoidal function (see Figures 7N, 7O, and 7P).

[0169] The illustrated waves are merely illustrative. It is contemplated that other types of waveforms may be generated, such as pulses or other shapes. In some embodiments, the stimulation waveform comprises a single pulse having a duration of 1 to 10 qs.

[0170] Other stimulation pulse control parameters may be controlled, for example, in feedback mechanisms, such as the electric field strength at the electrode, the DC offset, the tissue temperature, the cooling mechanism parameter, and the treatment duration. In some embodiments, the stimulation device and system are configured to control electrical stimulation based on observed or measured temporal and / or spatial derivatives of voltage, current, power, and temperature (e.g., the rate of change of temperature over time).In some embodiments, two or more strategies of current-controlled stimulation, voltage-controlled stimulation, power-controlled stimulation, and temperature-controlled stimulation may be performed in combination to deliver to the target nervous and non-nervous tissue of the nervous structure. The amplitude, waveform, frequency, DC offset, duty cycle, and duration parameters may be adjusted for stimulations such as current-controlled stimulation, voltage-controlled stimulation, power-controlled stimulation, and / or temperature-controlled stimulation, or a combination thereof.

[0171] Indeed, the stimulation parameters can be optimized to selectively inhibit pain perception while preserving nerve activity responsible for motor activity, low-threshold sensory function, and proprioception. For example, the stimulation parameters can be optimized to attenuate or abolish the activity of myelinated Aδ and unmyelinated C fibers while preserving (e.g., without attenuation) nerve activity in nerve fibers responsible for motor activity, low-threshold sensory function, or proprioception.

[0172] The amplitude and other parameters of the stimulation waveform may be adjusted to preferentially or optimally modulate activity in a desired region of a nerve (e.g., specific regions of a nerve relative to the complete cross-section of the nerve), as will be described in more detail below. The stimulation waveform may also include parameter changes that influence and reduce the apparent response (e.g., a pulsing sensation at the nerve structure, a motor response in a muscle adjacent to the target nerve, such as muscle spasm or muscle contractions) and activation of the nerve tissue at the onset of stimulation either at the beginning of the continuous waveform or at the beginning of each stimulation burst during intermittent stimulation. The parameters of the stimulation waveform may also be adjusted to control the duration and time course of pain inhibition that will be achieved after treatment and to ensure that adequate pain inhibition is achieved with a single treatment.

[0173] The stimulation waveform parameters may be adjusted to allow treatment of larger nerves (e.g., greater than about 2.5 mm in diameter) and larger nerve structures or nerve structures of different shapes and sizes, as well as the composition of the nervous and non-nervous tissues, for example, by increasing the amplitude or adjusting other parameters of the stimulation waveform that result in an increase in the spatial size and shape of the electric field. Some nerve structures, such as the spinal cord and certain ganglia or plexuses, are large in nature and treatment of these large structures is made possible by adjusting the waveform parameters.

[0174] The parameters of the stimulation waveform may also be adjusted to allow for non-damaging treatment and pain inhibition. Hardware and software may also be included to control the amount of direct current delivered simultaneously with the waveform. The controller 130 may include, for example, a current controller or a voltage controller to adjust the amount of direct current or voltage delivered simultaneously with the electrical signal.

[0175] The device and method of the present invention may be used to selectively and reversibly modulate nerve signal transmission, for example by inhibiting or blocking nerve signal transmission, to inhibit pain perception for a period of about 1 day to about 30 days. Preferably, pain perception is inhibited for a period of about 5 days to about 30 days. Reversibility of nerve signal transmission and subsequent recovery of function after the appropriate time period following treatment are important, particularly for acute post-operative pain. The parameters of the stimulation waveform may be adjusted to adjust the expected duration of pain inhibition and to ensure that pain inhibition does not last longer as desired. In one example, the duty cycle, pulse amplitude, and treatment duration (see, e.g., Figures 10 and 11) may be adjusted to produce a desired reversibility of nerve signal inhibition (see, e.g., Figures 10 and 11). In another example, temperature control at the treatment site may be used to produce a desired selectivity of modulation of nerve signal transmission (see, e.g., Figures 10 and H).

[0176] As mentioned above, the device and method of the present invention, including the waveform parameters and their adjustment, can selectively inhibit acute pain (such as post-operative pain) for a period ranging from a few days to several weeks after the procedure. However, it should also be understood that the device and method of the present invention, including the waveform parameters and their adjustment, can also be used to provide therapeutic treatment for chronic pain conditions. Therapeutic treatment of chronic pain may include continuous preemptive delivery of signals, or abortive delivery on demand when episodes of chronic pain are experienced. This may be achieved by percutaneous, partially implanted, and implanted approaches.

[0177] Compared to other methods of modulating the activity of a nerve structure using an electrical signal, the system and method of the present invention are capable of providing selective and reversible pain relief for periods of days to weeks with a single treatment / application of the electrical signal. Other treatment modalities require repeated treatments over a period of days to provide significant and sustained pain relief, particularly with respect to the treatment of large nerves. For example, pulsed radiofrequency, frequently used to treat pain in small nerves, uses intermittent pulses of a 45 V radiofrequency signal to stimulate the target nerve. The pulse is used in this case to avoid temperatures at the treatment site that could damage or destroy the nerve tissue.In contrast, the stimulation parameters of the present disclosure allow for the application of a high voltage and frequency waveform that does not have the temperature limitations associated with a pulsed RF signal. Adjusting the stimulation waveform parameters allows for control over the application of the electrical signal to ensure that adequate pain inhibition is achieved with a single application, while avoiding tissue damage.

[0178] For example, a system may be configured to deliver the electrical signal (also referred to as "electrical stimulation" in this disclosure) to the treatment site with a frequency range of about 100 kHz to about 1 MHz, from about 200 kHz to about 800 kHz, from about 400 kHz to about 600 kHz, and from about 450 kHz to about 550 kHz. In an exemplary system, the electrical stimulation delivered to the treatment site is at least 500 kHz. The electrical signal delivered to the treatment site has an amplitude range of > 5 mA (peak to center, corresponding to 10 mA peak to peak) and < 1.25 A (peak to center, corresponding to 2.5 A peak to peak). In an exemplary system, the electrical signal has an amplitude between 50 mA and 500 mA, 500 mA and 1 A, 1 A and 1.5 A, 1.5 A and 2 A, or 2 A and 2.5 A. In an exemplary system where the electrical stimulation is delivered transmucosally, the electrical signal has an amplitude range between about 10 mA and about 5,000 mA (peak-to-peak). The electrical signal delivered to the treatment site has an amplitude range of > 10 V and < 500 V (peak-to-center, corresponding to 20 to 1,000 V peak-to-peak).In an exemplary system, the electrical signal has an amplitude between 10 V and 1000 V, 20 V and 100 V, 100 V and 200 V, 200 V and 300 V, 300 V and 400 V, or 400 V and 500 V. In an exemplary system where the electrical stimulation is delivered transmucosally, the electrical signal delivered to the treatment site has an amplitude range of >10 V and <1000 V (peak-to-peak). In an exemplary system, the electrical stimulation delivered to the treatment site has a power between about 0.1 W and about 1250 W.

[0179] The electrical signal delivered to the treatment site may have a sine waveform, a square waveform, a triangular waveform, a frequency modulated waveform, a pulse (e.g., an amplitude modulated waveform or a pulse-shaped waveform), and / or additive combinations thereof. An example of a frequency modulated waveform is a chirp. An example of an amplitude modulated waveform is a wavelet. In another example system, the electrical signal delivered to the treatment site has an arbitrary waveform. In another example system, the electrical signal may have a combination of the previously mentioned waveforms. Repeated delivery of the waveform implies that a waveform is delivered repeatedly at a specified repetition rate. The waveform of the electrical signal may be delivered continuously or intermittently.Continuous delivery involves the waveform being delivered at a specified waveform rate continuously, without interruption. Intermittent delivery involves the waveform being delivered at a specified waveform rate during time envelopes separated by pauses during which no stimulation is delivered. For continuous delivery, the duty cycle is 100% (e.g., via the chirp function). For intermittent delivery, the duty cycle is in the range of about 0.1% to about 99%, preferably 0.5% to 25%. The term duty cycle refers to a period during which . the pulse has multiple oscillations with a predefined frequency. For intermittent delivery, the electrical signal has an inter-envelope width of about 1 ms to about 999 ms, preferably 70 to 999 ms, the inter-envelope width being defined as the duration between the end of one envelope and the start of the next envelope. In one example, the electrical signal has a pulse width of 30 ms delivered at 10 kHz.

[0180] In an example treatment, the electrical signal is delivered for a treatment duration < 30 minutes, preferably < 15 minutes. In an example system, the electrical signal is delivered for a treatment duration < 1 minute, from 1 minute to 5 minutes, from 5 minutes to 10 minutes, from 10 minutes to 15 minutes, from 15 minutes to 20 minutes, from 20 minutes to 25 minutes or from 25 minutes to 30 minutes.

[0181] As described below, the controller 130 is adjustable to apply the electrical stimulation while maintaining the tissue temperature between about 5°C and about 60°C. That is, the electrical signal may have a tissue temperature that has an amplitude between about 5°C and about 60°C.

[0182] The electrical signal delivered to the treatment site may be current controlled, voltage controlled, power controlled, and / or temperature controlled. The electrical signal comprises a continuous charge-balanced waveform or pulse, or an additive combination thereof. Alternatively, the electrical signal comprises an uncharged balanced waveform or pulse, or an additive combination thereof.

[0183] The strength of the electric field generated at the target site is greater than 10 kV / m. Electrical stimulation delivered to the treatment site generates or induces an electric field strength at the target site and / or the electrode(s) of between about 20 kV / m and about 2,000 kV / m. The electric field generated at the target site is between 20 kV / m and 2,000 kV / m at its temporal peak, from 25 kV / m to 500 kV / m or from 50 kV / m to 400 kV / m. In a transmucosal application, the electrical stimulation generates or induces an electric field strength at the target site and / or the electrode, preferably between about 20 V / m and about 1,000,000 V / m. The electric field strength varies depending on the distance from the electrode, the shape of the electrode, and other factors such as the conductivity of different tissues near the electrode. Adjusting the waveform parameters of the stimulation waveform allows control of the spatiotemporal electric field within the tissue and at the interface of the electrode with the tissue. Adjusting the waveform parameters of the stimulation waveform also allows control of the spatiotemporal thermal field within the tissue and at the interface of the electrode with the tissue. The spatiotemporal variations and levels of the electric field and the thermal field are important factors in the production of the desired reversible selective inhibition of pain in target neural structures. In addition, a cooling mechanism, as discussed in detail below, implemented in concert with the waveform and other aspects of stimulation such as the electrode, allows for the control and reduction of the spatiotemporal thermal field independent or semi-independent of the electric field. The separation of these two important variables ultimately allows for the delivery of a selective, reversible, and adjustable treatment that does not damage the neural tissue.

[0184] In addition to selective treatment of different fiber types, the parameters of the electrical stimulation and the induced electric field as well as the parameters of the electrical waveform can also be adjusted to preferentially modulate the transmission of the nerve signal in a desired region of the nerve structure, where the desired region of the nerve structure is a portion of the nerve structure less than its full cross-section.

[0185] The electrical stimulation may also be adjusted to reduce the apparent response (e.g., a pulse sensation at the nerve structure, a motor response in a muscle adjacent to the target nerve, such as a muscle spasm or contraction, and activation of the nerve structure upon delivery of electrical stimulation to the nerve structure.

[0186] EXAMPLE OF COOLING MECHANISM

[0187] It is also contemplated that the stimulation device 100 may include a cooling mechanism to prevent damage to the patient's tissue when delivering electrical stimulation. The cooling mechanism may be integrated with the electrode 120 and / or a component separate from the electrode 120 that may be coupled to the electrode or positioned at the treatment site separate from the electrode 120. The cooling mechanism may be controlled by the controller 130 or include a separate controller to direct its operation. The cooling mechanism is used to provide a cooling effect on the contact surface of the stimulation device 100 and / or on the contact surface of the electrode 120 and / or in the tissue proximate to the treatment site.

[0188] It will be apparent to those skilled in the art that the delivery of electrical stimulation waveforms to tissue may result in heating of the tissue adjacent to the delivery electrode 120. When the heating of the tissue is excessive, thermal damage to the tissue may be created. It is an objective of the present invention to produce selective and reversible inhibition of pain perception while preserving other sensory and motor functions, as well as proprioception. Thermal injury to tissue has been deliberately used to eliminate or inhibit the transmission of nerve action potentials. However, these approaches do not preserve sensory and motor functions, or proprioception. Additionally, tissue cooling has been used with thermal ablations, for example with cooled radiofrequency ablations, to allow for increased power dissipation in the tissue, allowing for increased power of an RF waveform and the creation of a larger thermal injury. However, these cooled RF approaches aim to raise the tissue temperature to at least 60-90°C in order to create a thermal injury in the tissue. In contrast, the present invention contemplates the use of a cooling mechanism that will preserve tissue below thermal damage levels while allowing for the delivery of an electrical signal that can result in pain inhibition while preserving the sensory, motor, and proprioceptive functions of the nerve structure.

[0189] The cooling mechanism creates a cooling effect that prevents damage to the patient's tissue when electrical stimulation is delivered by keeping the patient's tissue temperatures below a tissue-destructive temperature, e.g., lower temperatures that may cause thermal damage to the tissue (e.g., avoiding temperatures that exceed 42-45°C for several seconds). The cooling mechanism maintains the temperature of the contact surface of the stimulation device 100 and / or the electrode 120 below a tissue-destructive temperature in response to feedback information received from the electrode 120 and / or input from the patient and / or the operator. The feedback information includes measured temperature data received from a temperature sensor 210 coupled to the stimulation device 100.The temperature sensor 210 may measure the temperature of the contact surface of the electrode 120 and / or the temperature of the patient's tissue adjacent to the contact surface of the electrode 120. The temperature sensor 210 is electrically coupled to the controller 130 and provides feedback information regarding the measured temperature. As described below, in response to the temperature feedback information, the operation of the cooling mechanism and / or parameters of the electrical stimulation may be adjusted to control the temperature at the contact surface of the electrode 120, thereby reducing the temperature of the adjacent patient's tissue.

[0190] In one example, the cooling mechanism may include a pump that circulates a cooling fluid such as a pressurized gas or fluid (e.g., carbon dioxide, nitrogen, water, propylene glycol, ethylene glycol, salt water, or mixtures thereof) through the electrode 120 via conduits 160 provided in the wires (L) (see Figures 3A-3E). The circulating gas / fluid serves to remove heat from the electrode 120, the treatment site tissue, and neighboring tissue. This gas / fluid may be delivered at the temperature ambient or can be cooled below ambient temperature using an incorporated gas / fluid cooling unit or by using ice or other cooling mechanisms. Cooling of the gas / fluid can be carried out before and during processing. A thermally insulating covering or sheath can also be incorporated around the wires (L) to prevent heating of the coolant by heat transfer to the ambient environment.

[0191] In another example, the cooling mechanism includes a heat transfer material provided in contact with the treatment site tissue and / or the electrode 120. The heat transfer material may be disposed within the electrode 120 / leads (L), on an exterior surface of the electrode 120, and / or on an introducer device. The heat transfer material acts as a heat sink by removing heat from the electrode 120, the treatment site tissue, and neighboring tissue.The heat transfer material may include a material with high thermal conductivity (e.g., a metal such as aluminum, a ceramic material, a conductive polymer), a material with high heat storage capacity (e.g., good thermal mass, such as materials with high specific heat capacity, high heat capacity per unit mass, high volumetric heat capacity, and / or high heat capacity per unit volume), and / or one or more Peltier circuits, or a combination thereof. The heat transfer material may also include a phase change material that can change phase at a temperature between about 40°C and 100°C. An example of a phase change material includes a paraffin wax provided in a pathway that extends from the electrode 120 / treatment site to ambient air.Heat exchange between the paraffin wax and ambient air serves to remove heat from the electrode 120 / treatment site and surrounding tissue. Examples of additional cooling mechanisms are described in US application 62 / 403,876, filed October 4, 2016, entitled “Cooled RF Probes.”

[0192] In addition to preventing tissue damage, the cooling mechanism allows for selective inhibition of pain. For example, non-selective inhibition of pain, in which a non-painful or pro-prioceptive motor or sensory function is also inhibited, can be observed when temperatures are not below the desired threshold (such as 42-45°C for several seconds). Preserving the target tissue below such a thermal threshold by means of a cooling mechanism allows for selective inhibition of pain without modulating or inhibiting other functions of the nerve structure. Thus, the temperature of the electrode and tissue is an important parameter that can be adjusted by means of the cooling mechanism to allow for selectivity of pain inhibition. pain.

[0193] Use of the cooling mechanism also allows for treatment of nerve structures of varying shapes, sizes, and compositions. For example, it may be necessary to increase the size of the spatial electric field generated by the electrical waveform in the tissue to encompass larger nerve structures such as large peripheral nerves, cranial nerves, ganglia, autonomic nerves, portions of the spinal cord, and plexuses. One method for increasing the size of the spatial electric field is to increase the amplitude of the electrical waveform. Use of the cooling mechanism allows delivery of an electrical waveform with a higher amplitude while maintaining the tissue at thermal levels that prevent thermal damage.For example, when the stimulation device 100 treats peripheral nerves with a diameter greater than 2.5 mm, the use of the cooling mechanism allows the electrical waveform parameters, including amplitude, to be adjusted to levels high enough to treat the larger nerve target without causing thermal damage to the nerve structure. In another example, the nerve structure, such as the spinal cord or ganglia (e.g., gasserian ganglion, sphenopalatine ganglion (SPG)), may be composed of and surrounded by various tissues with different thermal and electrical conductivities.In this case, the cooling mechanism allows for the delivery of a therapeutic waveform that produces the desired selective and reversible inhibition of pain in a desired region of the nerve structure, while preventing thermal damage to sites (including the nerve structure and its surrounding tissues) subject to heating.

[0194] Further, use of the cooling mechanism allows the spatial field of the tissue being treated by the electrical signal to be adjusted to allow modulation of nerve signal transmission in a desired region of the nerve structure, the desired region of the nerve structure being a portion of the nerve structure smaller than its full cross-sectional area. Cooling may be applied to tissues proximate to the electrode 120 or to tissues neighboring the target treatment site to prevent tissue temperatures from exceeding a desired threshold level. For example, stimulation delivered via an electrode without cooling may produce a thermal field in the tissue that would be thermally damaging at some locations in the tissue.The use and placement of the cooling mechanism at locations likely to cause thermal damage to the tissue allows for non-damaging treatment and adjustment of the spatial field of the tissue being treated by the electrical signal. In another example, thermal pulses in the tissue may be produced for short periods (e.g., less than one second). The cooling mechanism allows for the reduction of these pulses. thermals below a threshold level at specific locations within the tissue to allow adjustment of the spatial field of the tissue treated by the electrical signal. In another example, the cooling and electrical waveform parameters can be adjusted simultaneously to allow treatment of a nerve structure (treatment of a portion of the nerve structure less than its full cross-sectional area or treatment of a full cross-sectional area of ​​the nerve structure) without causing thermal damage.

[0195] EXAMPLE OF ELECTRODE

[0196] Figures 3A-3G provide schematic representations of various exemplary electrodes 120 for delivering electrical stimulation to the target nerve structure. The electrodes 120 of Figures 3A-3E and 3G are in the form of one or more percutaneous electrodes configured to be placed proximate (e.g., the electrode is within about 1 cm, about 5 cm, or within 2 mm of the nervous system structure, without contacting the nervous system structure), around, and / or in contact with a target nerve. The exemplary electrodes are illustrated in Figures 3A-3E and 3G in a side perspective view. Exemplary percutaneous electrodes are also described in U.S. Patent Application No. 15 / 501,450, filed February 3, 2017, entitled “Selective Nerve Fiber Block Method and System.”

[0197] Each electrode used in a bipolar or multipolar manner includes at least one anode region and at least one cathode region positioned proximate / in contact with the target nerve "N". The unipolar electrode 120 illustrated in Figure 3A may include a cathode located proximate a nerve and a return electrode (e.g., an anode) positioned a distance away (e.g., as a patch electrode on the skin surface). The bipolar and multipolar electrode configurations, as illustrated in Figure 3B, include at least one cathode and one anode proximate the nerve. The shape and size of the electrodes, as well as the spacing between electrodes, are specific to the contour of the electric field and thermal fields surrounding and penetrating the nerve to allow for selective and reversible modulation of the target nerve structure.Figure 3C provides another example of a percutaneous electrode 120 having a hook or J-shape. As illustrated in Figure 3C, the electrode 120 is sized and configured to conform to the target neural structure laterally within the convex portion of the hook shape, such that, once positioned, the neural structure is retained near the electrode 120 and contact between the neural structure and the contacts of the electrode 150 is ensured. As illustrated in Figure 3C, the electrode 120 includes two electrical contacts, a first contact 150 provided on the curved hook / J-shaped distal end of the electrode 120 and a second contact 150 provided on the body. elongated main electrode 120. Such an electrode may be configured for insertion via an introducer and such that the hook / J-shaped portion of the electrode tip is bent within the introducer, thereby providing a reduced profile. Upon exiting the introducer, the bent portion of the electrode 120 expands and curves around the surface of the nerve structure. Figure 3D illustrates an exemplary electrode 120 in which the electrode tip defines a generally hemispherical shape and provides a generally uniform nerve contact surface. The electrode may include an expandable conductive surface that, when inserted through a small diameter introducer, is confined / non-expandable and provides a reduced profile.Upon exiting the introducer device, the expandable conductive surface expands to fit around the surface (or a portion of the surface) of the target neural structure. Figure 3E illustrates an exemplary electrode 120 having a V- or U-shape. As illustrated in Figure 3E, the electrode 120 is sized and configured to be placed so that the target nerve structure is positioned laterally within the convex portion of the V / U-shape. Once located at the treatment site, the nerve structure is positioned within the convex portion of the electrode 120 to maintain contact with the contacts 150 on longitudinally opposite sides of the nerve structure.

[0198] [Fig. 3G] provides another example of a percutaneous electrode 120 having a distal end extending at an angle relative to the main body portion of the electrode 120. This bipolar configuration includes two electrical contacts 150 positioned along the elongated body of the electrode forming a cathode and an anode in the vicinity of the nerve (N). As in each of the electrodes shown in Figures 3A-3E and 3G, the length of the electrical contacts may be between 1 and 50 mm, depending on the size of the target nerve structure / nerve. For example, the length of the electrical contacts may be in the range of about 1 mm to about 30 mm. In another example, the length of the electrical contacts may be between about 2 mm and about 20 mm. In another example, the length of the electrical contacts may be between about 2 mm and about 15 mm.In yet another example, the length of the electrical contacts may be between about 5 mm and 10 mm. It is contemplated that the length of each of the electrical contacts 150 included on an electrode 120 / elongated body of the electrode 120 may be the same or different. For example, each of the electrical contacts 150 shown on the electrode 120 of Figure 3E has the same length to generate a coherent and uninformed electric field relative to the nerve. In the example electrode 120 shown in [Fig.3G], the length of the electrical contacts 150 varies along the electrode 120. In particular, the length of the distal electrical contact . 150a located at the distal end 122 of the electrode 120 is greater than the length of the proximal electrode 150b (positioned along the main body 124 of the electrode 120 between the distal electrical contact 150a and a proximal contact end of the electrode 120). Generally, the distal electrical contact 150a may be at least twice the length of the proximal electrical contact 150b. In one example, the distal electrical contact 150a may be about 10 mm long and the proximal electrical contact 150b may be about 4 mm long. In another example, the surface area of ​​the distal electrical contact 150a and the proximal electrical contact 150b may be matched, while the length of the electrodes may be different.For example, if the proximal electrical contact has a larger circumference / circumferential width than the distal electrical contact, then the proximal electrical contact could achieve a suitable surface area by having a shorter length than the distal electrical contact.

[0199] As illustrated in [Fig. 3G], the electrode 120 has an elongated body in which the distal end 122 of the electrode 120 extends at an angle relative to the longitudinal axis of the main body portion of the electrode 120. It is contemplated that the angle of the distal end portion 122 may be between about 0 and about 50 degrees. The angle of the distal end portion 122 is between about 5 and about 15 degrees relative to the main body 124 / major axis of the electrode 120. The distal end portion 122 of the electrode 120, beyond the bend, may extend in a straight line (as illustrated in [Fig. 3G]). It is also contemplated that the distal end portion 122 may be curved or include a curved surface. As illustrated in [Fig.3G], the distal electrical contact 150a is located along the distal end portion 122 and the proximal electrical contact 150b is located along the elongated main body portion 124 of the electrode 120. In this orientation, the distal electrical contact 150a is sized and configured to interface with the targeted nerve and the proximal electrical contact 150b is sized and configured to be positioned adjacent to subcutaneous tissue, e.g., fat, fascia, muscle. In this configuration, the tissue resistance between the electrode 120 / electrical contacts 150 is increased, resulting in higher delivered voltages and lower currents, with the delivery of a lower current providing less heating of the tissue.

[0200] [Fig.3F] illustrates an exemplary electrode 120 for use in treating a nervous structure and any overlying mucosal tissue. Specifically, the electrode of [Fig.3F] is suitable for use in delivering electrical stimulation to the gassian ganglion and / or the sphenopalatine ganglion (SPG). The stimulation device includes an elongated body portion 220 sized and configured to be advanced into the patient's nostril and along the upper edge of the middle nasal turbinate. One or more electrodes 120 are provided at a distal end of the elongated body portion 220. The electrode 120 has a contact surface having a size corresponding to a size of the SPG such that electrical stimulation provided at the electrode 120 can simultaneously modulate the entire SPG and also provide uniform pressure on a mucosal layer near / overlying the SPG. In general, the contact area of ​​the electrode 120 is between 1.57 to 56 mm2. The width of the contact surface of the electrode 120 is between at least 1 mm and 6 mm. In one example, the contact surface of the electrode 120 has an elongated triangular, spiked ball, or half-ball or flat circular shape. As described above, the electrode of [Fig.3F] is configured to be advanced through the nasal cavity to a position adjacent to the sphenopalatine ganglion (SPG). As such, the elongated body portion 220 ranges from 5 cm long to 20 cm long.The elongated body portion 220 has a contour corresponding to an upper edge of the middle nasal turbinate. To facilitate delivery and positioning, it is also contemplated that the elongated body portion 220 is comprised of a flexible material. Although not illustrated, it is contemplated that the stimulation device 100 and / or the electrode 120 may be sized and configured for placement in the patient's mouth. For example, the electrode 120 may be located on a mouthpiece fitted around the gums and teeth such that the electrode 120 is positioned over the gingival tissue (e.g., at the gum line). The electrode 120 may be located on the mouthpiece such that, when worn, it is adjacent to at least one peripheral ganglion or nerve, including, for example, a lingual nerve, an alveolar nerve, and a buccal nerve.

[0201] As described above, the electrode 120 may include one or more contacts 150 for delivering the electrical stimulation to the treatment area / target nerve structure. A contact 150 is defined as a portion of the electrode 120 intended to form the interface between the electrode 120 and the tissue at which the electrical stimulation is delivered (so as to generate an electric field in the tissue). The configurations of the electrode 120 and a contact 150 may be designed to maximize and direct the electric field and current flow into the target nerve structure, and deliver a therapeutic dose of electrical stimulation to nerves of various sizes, shapes, and compositions, without unwanted stimulation of nearby tissue, while ensuring reliable placement of the electrode 120 relative to the neural structure for optimal therapeutic effect.

[0202] Relevant electrode design factors include the number of contacts, size, geometry, orientation, material, electrolytic medium, delivery mode (e.g., unipolar, bipolar, multipolar), and return path. Adjusting and tuning these factors allows the electric field and thermal field to be guided through the neural structure or a portion of the appropriate neural structure to produce selective and reversible inhibition of pain. In addition, adjustment and tuning of these factors allows the electric field and thermal field to be directed through the appropriate neural structure or part of the neural structure to allow the therapeutic treatment to be effectively delivered in a single application and to adjust the time to reversibility of the treatment effects. Tuning and adjustment of these factors also allows the electric and thermal fields to be modulated to treat the entire cross-sectional area of ​​large neural structures such as large peripheral nerves (> 2.5 mm in diameter), cranial nerves, ganglia, autonomic nerves, plexuses, and the spinal cord, as well as to treat parts of large and small neural structures.For example, the size and shape of electrical contacts or the number of electrical contacts can be adjusted to optimize surface contact with a large nerve. Similarly, the size and shape of electrical contacts or the number of electrical contacts can be adjusted to optimize surface contact / electrical stimulation transmission to a nerve structure underlying mucosal tissue.

[0203] The number of electrode contacts, size, geometry, orientation, material, electrolytic medium, mode of delivery (e.g., unipolar, bipolar, multipolar), and return path may also be adjusted to avoid thermal damage to the tissue. These factors influence the thermal field produced by the electrical waveform, including the occurrence of thermal damage at certain locations in the tissue relative to the electrodes, and adjustment of these factors, including adjustment in the context of cooling mechanisms and waveform adjustment, helps avoid thermal damage to the tissue.

[0204] For example, the electrode 120 is sized and configured to maximize and direct the electric field created by the electrical stimulation delivered to the target nerve structure. The electrode electrical contact 150 may have a surface area ranging from about 1 mm2 to about 100 mm2 to accommodate the sizes of the electric and thermal fields that are necessary to provide therapeutic treatment to portions of small and large nerve structures, as well as the entire cross-sectional area of ​​small and large nerve structures. Preferably, the electrode contact 150 has a surface area ranging from about 2.5 mm2 to 45 mm2. Electrical contacts that are too large may include portions of the contact surface 150 that are not in contact with the neural structure and, therefore, serve as a bypass pathway through which current can flow.When designing electrodes for therapeutic treatment of a nerve structure, shunt current is often discouraged because it increases the current required to power the device. control in order to produce the therapeutic effect. As illustrated in [Fig. 3G], the electrical contact 150 may also define a smooth, curvilinear-shaped perimeter including, for example, circular or oval-shaped contact surfaces. The sharp edges of rectilinear-shaped contacts, for example, square or rectangular-shaped contacts, may result in increased current densities and thermal heating. However, it is contemplated that rectilinear-shaped contacts 150 may be used when specifically sized and located on the electrode 120 to take advantage of increased current densities and thermal heating.Thus, the dimensions and shapes of the electrical contacts are optimized based on the desire to target the delivery of the therapeutic electric field and the thermal field to the nerve structure while maintaining the necessary current flow from the control device to produce the therapeutic effects.

[0205] In another example, the electrode 120 may include at least two contacts 150 that operate dependently in a multipolar manner to enable steering and / or focusing of the resulting electric field current. In another example, the electrode 120 includes at least two contacts 150 (e.g., two contacts 150 on the same electrode 120 or multiple electrodes 120 with their corresponding contacts 150) that operate independently. In this manner, the electrical stimulation delivered by each of the electrodes 120 may be alternated such that the total electrical stimulation delivered to the neural structure is delivered in less (half) the time.Specifically, each of the separate electrodes 120 may deliver an intermittent electrical stimulation signal, wherein electrical stimulation of the first electrode alternates with electrical stimulation of the second electrode, e.g., an "on cycle" of the first electrical stimulation delivery occurs during an "off cycle" of the second electrical stimulation and an "on cycle" of the second electrical stimulation delivery occurs during an "off cycle" of the first electrical stimulation.

[0206] In another example, the electrode 120 may include multiple electrode contacts 150 that may be selected to direct the electrical and thermal fields by selecting one or more electrode contacts 150 to be used as an anode and one or more other electrode contacts to be used as a cathode. Selecting different combinations of electrode contacts allows for adjustment of the shape and size of the electrical field and thermal field. For example, with respect to the electrode 120 of [Fig. 3G], the distal and proximal electrical contacts 150a, 150b may be positioned on the same side of the elongated body / electrode 120. As such, the electrical contacts 150a, 150b do not deliver electrical energy circumferentially around the portion of the circumference of the elongated body electrode 120 without electrical contacts (e.g., the electrical contacts 150a, 150b do not do not deliver electrical energy circumferentially relative to the short axis of the electrode body 120), thereby providing voltage field shaping and current direction of the delivered electrical stimulation. A brief test pulse of electrical stimulation may be delivered via a subset of contacts to determine nerve proximity and coverage, and more contacts may be added until sufficient contact with the nerve is verified (e.g., by monitoring leg motor output by movement or electromyography).

[0207] A resistor may be placed in series with the electrical circuit of the electrical contacts 150 of the electrode 120. For example, with respect to the electrode 120 of [Fig. 3G], a resistor may be positioned in series with one or both of the electrical contacts 150a, 150b. The resistor will increase the stimulation impedance and voltage delivered by the generator 140 at or below the desired setpoint temperature (e.g., the tissue-destructive temperature) and reduce the stimulation current and thermal variations. Similarly, the electrical contacts 150 may be constructed from a high-impedance or high-capacitance material. For example, materials having an impedance or capacitance greater than stainless steel or platinum may be used to reduce the stimulation current and thermal variations while still allowing the delivery of a high voltage level.This will further increase the stimulation impedance and voltage delivered by the generator 140 at or below the desired setpoint temperature (e.g., tissue-destructive temperature) while reducing stimulation current and thermal variations.

[0208] Generally, electrical stimulation may be delivered to the target nerve structure using an electrode 120 that may be in the form of a percutaneous electrode array to temporarily and selectively modulate the activity of nerve fibers in the target nerve structure. For example, the electrode 120 may include an electrode array in the form of a paddle, a sleeve, a cylindrical catheter, or a needle, wire, or thin probe, configured to be introduced percutaneously through an opening in the patient's skin.In another example, for use in the treatment of head and facial pain (as described in more detail herein), the electrical stimulation may be delivered to the target nerve structure via and electrode 120 placed on mucosal tissue of a patient, e.g., an electrical probe sized and configured to be advanced transnasally to a target site proximate to the gassian ganglion and / or the sphenopalatine ganglion (SPG).

[0209] Additionally, electrical stimulation may be delivered to the target nerve structure via an electrode 120 implanted in the patient, for example for the treatment of chronic pain. In this case, the electrode 120 may be surgically implanted and may be placed in contact with or around the neural structure during a surgical procedure or during a minimally invasive implantation procedure. The electrode 120 may be secured to the neural structure and surrounding tissue using sutures or anchoring structures constructed on the electrode that secure the electrode to neural structures or nearby tissue.

[0210] The wire (L) comprises a means for transmitting electrical energy between the electrical stimulation device 100 and the electrode 120, for example via a conductive wire or cable. The wire (L) may be directly attached to the electrode 120 permanently or may be attachable and detachable using a conductive connector. In this case, compatible connectors would be present on the electrode 120 and on the wire (L). The wire may be directly attached to the electrical stimulation device 100 / signal generator 140 permanently or may be attachable and detachable using a conductive connector. In this case, compatible connectors would be present on the electrical stimulation device 100 / signal generator 140 and on the wire (L). The wire (L) may also include fluid / gas transmission pathways, such as conduits 160 used to transmit a fluid / gas used to cool the electrode(s) 120.Fluid transmission lines 160 may be connected to the electrode 120 and a cooling device directly or via attachable / detachable connectors. The wire (L) may also be contoured to provide an optimal shape for placement of the electrode 120, for example to allow navigation of the electrode to an ideal location near the neural structure and to navigate around obstacles or tissues presenting a partial barrier between the insertion point and the target neural structure.

[0211] The wire (L) and electrode 120 may be placed using wire introduction tools, such as cannulas, guide wires, introducer needles, and trocars. Particularly for percutaneous placement, these wire and electrode introduction tools may be used to navigate through the skin and underlying tissue to a position near the target neural structure. The introduction tool may also be used to enable the introduction / placement of any necessary contacts 150 and other electrode components near the target neural structure.The wire (L), electrode, and introduction tools allow the electrode to be placed near large and small target neural structures, including peripheral nerves, cranial nerves, ganglia, autonomic nerves, plexuses, and the spinal cord, and also allow for proper interfacing between the electrode(s) and these target neural structures, which helps produce selective and reversible inhibition of pain perception. The wire (L), electrode, and introduction tools also allow the electrode 120 to be placed in percutaneous use cases, for example. for acute pain, and for implanted use, for example for chronic pain.

[0212] Figure 4A provides a schematic representation of an exemplary percutaneous electrode 120 (e.g., [Fig. 3G]) positioned adjacent to a target neural structure, e.g., a peripheral nerve through an opening in the patient's skin. The electrode may be comprised of a single needle-shaped shaft with two electrical contacts 150. In this example, the distal electrical contact 150a serves as an active electrical contact proximate the target neural structure (N) and the proximal electrical contact 150b serves as a return electrode. As described above, the material of the shaft of the electrode 120 may be selected based on a desired thermal conductivity and / or thermal mass (e.g., to allow the electrode 120 to act as a heat sink, which may allow treatment waveforms to be delivered with a higher current or voltage without increasing the temperature of the tissue).The material of the electrode shaft 120 may also be selected based on a desire for the probe to be visible by ultrasound imaging (e.g., an echogenic material) or by fluoroscopic imaging.

[0213] The distance (A to B) between the skin surface and the proximal electrical contact 150b (return contact) may be optimized to reduce the risk of damage to the skin or subcutaneous tissue. For example, the distance A to B may range from about 0 to about 40 mm. In another example, the distance AB may range from about 0 to about 20 mm. In another example, the distance A to B may range from about 5 mm to about 15 mm. In another example, the distance A to B may range from about 10 mm to about 15 mm.The distance (C to D) between the proximal electrical contact 150b (return contact) and the curvature and / or distance (C to E) between the proximal electrical contact 105b and the distal electrical contact 150a (active contact) is chosen to optimize treatment results, for example, by shaping the voltage field to be preferentially oriented toward the target neural structure, or for example, by concentrating thermal energy during the pulses of the therapy waveform, for example, by diverting thermal energy away from the target neural structure. In an exemplary system, the distances C to D and C to E will be between about 2 mm and about 50 mm. Preferably, the distances C to D and C to E will be between about 10 mm and about 30 mm.

[0214] The distance (C to D) between the proximal electrical contact 150b (return contact) and the curvature and / or the distance (C to E) between the proximal electrical contact 150b (return contact) and the distal electrical contact 150a (active contact) can be selected to allow the treatment of different target neural structures of different depths on patients with different anatomical configurations (e.g. example, different thicknesses of muscle, skin and fat layers, different depths to target neural structures, etc.). For example, the distance between the proximal electrical contact 150b (return contact) and the bend or distal electrical contact 150a (active contact) (C to D or C to E) may be selected so that the distal electrical contact 150a (active contact) can be placed near a variety of target neural structures on a variety of different patients with a variety of different anatomical configurations, but such that the distance (A to B) between the skin and the proximal electrical contact 150b (return contact) is sufficient to allow efficient delivery of energy without damaging the skin or other subcutaneous tissues.In another example, the electrode may have an adjustable distance (C to D or C to E) such that the proximal electrode contact 150b (return contact) may be repeatedly placed in a desired anatomical location (e.g., in the adipose layer or at a fixed distance under the skin) regardless of the depth of the target neural structure.

[0215] The distance (F to G) between the distal electrical contact 150a (active contact) and the distal end of the electrode 120 may be selected to reduce spatiotemporal thermal spikes when delivering the treatment waveform by avoiding current delivery via geometric structures on the contact 150a that may produce high current densities, such as a sharp pointed tip. In addition, the distance (F to G) between the distal electrical contact 150a (active contact) and the tip of the electrode 120 may be selected based on design and manufacturing considerations such as the choice of material for the electrode shaft and tip.For example, if the electrode shaft and tip are made of conductive material and are electrically or continuously connected to the distal electrical contact 150a (active contact), then the distal electrical contact 150a (active contact) may also include the electrode tip 120 (e.g., because the insulation on the sharp end may be removed upon penetration through tissue). Conversely, if the electrode shaft and tip are made of non-conductive material and are not electrically coupled to the distal electrical contact 150a (active contact), the distance (F to G) between the active contact and the electrode tip may be greater than 0 mm. The choice of this distance (F to G) may also be influenced by the desired echogenicity of different components of the probe.Additionally, the tip of the electrode 120 may be configured to be smooth, non-pointed, or blunt to minimize high current densities or overcome risks of insulation removal upon insertion.

[0216] The angle (a) of the distal end 122 of the electrode 120 may be selected to enable the guidance of the contacts 150 to the target neural structure (N) during insertion and placement of the electrode 120. This angle (a) also helps to direct the transmitting the therapeutic waveform to the target neural structure, for example, by directing the current flow through the target neural structure, causing the voltage field to be preferentially directed toward the target neural structure, and / or by focusing the thermal energy during the pulses of the therapeutic waveform toward the target neural structure.

[0217] The length (E to F) of the distal electrical contact 150a (active contact) may be chosen to cover the entire diameter of a target neural structure or to cover only a portion of the target neural structure (e.g., a fascicle or group of fascicles). In one embodiment, the length (E to F) of the distal electrical contact 150a (active contact) and the length (B to C) of the proximal electrical contact 150b (return contact) may be the same. In other embodiments, the length (B to C) of the proximal electrical contact 150b (return contact) may be greater than the length (E to F) of the distal electrical contact 150a (active contact). The longer proximal electrical contact 150b (return contact) may ensure that the current density at the return contact is less than the active contact (distal electrical contact 150a) (e.g., if the area of ​​the return contact is greater than that of the active contact).The longer return contact (proximal electrical contact 150b) may also reduce the risk of heat at the return contact (proximal electrical contact 150b) or near the skin and subcutaneous tissue. In another embodiment, the length (B to C) of the proximal electrical contact 150b (return contact) may be less than the length (E to F) of the distal electrical contact 150a (active contact). The longer active contact (distal electrical contact 150a) may increase the impedance of the therapeutic waveform circuit. A longer active contact (distal electrical contact 150a) may also be used to increase the voltage field at the active contact while maintaining or reducing the current delivered to the tissue or thermal heating of the tissue.Notably, increasing the impedance of the therapeutic waveform circuit may also be achieved, in whole or in part, by adding a resistive element, as mentioned above, to the active or return path in the electrode circuit 120. A resistive element may be added in line with an electrical cable or an electrical routing element that connects to an electrical contact 150. The cable itself may also act as the resistive element in the circuit.

[0218] Figure 4B provides a schematic cross-sectional view of the electrode 120 and the electrical contact 150 of Figure 4B. The active and / or return contact of the electrode 120 may also be oriented to have a contact arc length (|3) that is completely circumferential (360°) or, as illustrated in Figure 4B, a contact arc length (|3) that is only partially circumferential (<360°). In some embodiments, the contact arc length (|3) is less than 180°. Reducing the contact arc length (|3) can be used to further direct the transmission of the therapeutic waveform toward the target neural structure (N), for example, by directing current flow through the target neural structure, shaping the voltage field preferentially oriented toward the target neural structure, and / or focusing thermal energy during the therapy waveform pulses toward the target neural structure. In addition, reducing the contact arc length (|3) may also help reduce the amount of current that flows through pathways in the tissue that do not include the target neural structure (e.g., shunt currents) or reduce the exposure of non-target neural structure tissue to the voltage field provided by the therapeutic waveform. These measures may reduce the power consumption of the system and reduce risks to non-target tissue.In one example, the distal electrical contact 150a (active contact), closest to the nerve, has an arc length of less than 180° to reduce shunt currents and preferentially direct current toward the nerve, while the proximal electrical contact 105b (return contact), which is farthest from the nerve, has an arc length of greater than 180°. In this example, using a longer arc length for the return electrical contact allows the surfaces of the two contacts to be matched while minimizing the (longitudinal) length of the return contact, which may allow for an optimal separation distance between the two contacts.

[0219] The thickness (t) of the electrical contact 150 may also be specified to allow for the fabrication of electrodes 120 to a specified needle gauge while providing sufficient electrical contact mass to withstand mechanical and electrochemical stresses of the contact materials that may be experienced during use of the electrode 120. For example, the thickness (t) of the electrical contact 150 may be between 0.01 mils and 50 mils.

[0220] An electrode holder 126 may be incorporated into the design to help secure the electrode 120 and minimize movement of the electrode 120 after placement is complete. For example, an electrode holder 126 may help stabilize the position of the distal electrical contact 150a (active contact) relative to the target neural structure (N) during delivery of the therapeutic waveform. An electrode holder 126 may also allow a user to deliver the therapeutic waveform without the need to hold the electrode 120 in place for the duration of the waveform delivery. The wire (L) may include electrical cables, and the connectors of the electrode 120 may be used to make an electrical connection with the distal electrical contact 150a (active contact), the proximal electrical contact 150b (return contact), and with a temperature sensing element 210 (e.g., TC- and TC+).

[0221] Echogenic features, such as laser-etched or engraved materials mechanically, can also be incorporated at desired positions on the electrode to allow improved visualization under ultrasound imaging.

[0222] The temperature sensing element 210 (also referred to as a temperature sensor) may be selected to provide a desired accuracy (e.g., + / -2°C, or e.g., + / -1°C, or e.g., + / -0.5°C or e.g., + / -0.3°C) and a desired range (e.g., 0 to 100°C, or e.g., 20 to 80°C or e.g., 30 to 70°C). The accuracy of the thermocouple depends on the ambient temperature at the cold junctions as well as manufacturing factors. Additionally, the temperature sensing element 210 and the electrode 120 may be configured to provide a desired response speed in the temperature measurements (e.g., a time constant of 0 to 500 ms, or a time constant of 0 to 100 ms, or a time constant of 0 to 10 ms, or a time constant of 0 to 1 ms).The shape / size of a thermocouple junction as well as the specific heat capacity of the materials used in the electrode 120 and the thermocouple / temperature sensing element 210 can be designed to produce a desired temperature measurement response speed.

[0223] [Fig. 10] illustrates various exemplary bipolar electrical contact 150 / electrode 120 configurations. As will be described in more detail below, exemplary configurations A-D illustrate a single-body electrode 120. Exemplary configurations E-H illustrate a single-body electrode 120 having a concentric contact structure as described with respect to Figures 1 1A and 1 1B, the electrode 120 used in conjunction with a windowed introducer cannula 230. Exemplary configurations I-J illustrate a flexible electrode 120 used in conjunction with a curved introducer cannula 230. And exemplary configurations K-M illustrate a straight electrode 120 used in conjunction with a straight introducer cannula 210. It is contemplated that any of these configurations, individually or in combination, may be used on any of the electrodes 120 described herein.

[0224] As will be described below, exemplary configurations include single-body electrode 120 designs and multi-body electrode 120 designs. For example, configurations A-D and E-H illustrate exemplary single-body configurations, comprised of a single-electrode rod 120 including two electrical contacts 150. The tip of the electrode 120 may be rounded and smooth (e.g., A, E-H) or pointed (e.g., B-D). The proximal electrical contact 150b (return contact) may be fully circumferential (e.g., A and B) or partially circumferential (e.g., C-H). The distal electrical contact 150a (active contact) may be shaped into various different geometries for the purpose of including / excluding the tip of the electrode 120 as a contact. electrical and / or direct the therapeutic waveform to the target neural structure. A lumen may be incorporated into all designs to enable injection of fluid through the electrode 120. For example, the lumen may be used to deliver drug treatment to the treatment site (e.g., an analgesic) before, during, and / or after delivery of the electrical stimulation. In Example D, a sharp tip is avoided as part of the active contact by using a second body that does not have an electrical contact. In this case, a sharp introducer needle that protrudes from the central lumen extending through the electrode 120. Here, the sharp introducer needle may be removed after placement of the electrode 120 or when it is desired to inject fluid through the lumen.In examples E-H, a cannula 230 that does not have electrical contact is used to provide a path for insertion of the single-body electrode 120. This cannula 230 may be initially placed without the single-body electrode, for example, with the use of a sharp introducer needle. After placement, the introducer needle may be withdrawn and the electrode 120 may be inserted into the cannula 230. The cannula 230 may be used to provide window access 232 to the return or active contacts (e.g., window access to the return contact in examples E-F). The cannula may be curved or straight (curved for E-F, straight for G-H). The electrode may also be curved or straight (curved for G-H, straight for E-F).

[0225] Multi-body designs, such as the examples illustrated in I-M, are comprised of multiple rods having electrical contacts 150. In these examples, the return electrical contact 150a is provided on the cannula 230 and a second body 234 with the active electrical contact 150b is inserted through the central lumen of the cannula 230. A multi-body may be used to provide an electrode with an adjustable distance between the active and return electrical contacts. For example, the second body 234 may be moved longitudinally within the cannula 230 until a desired spacing between the active and return electrodes 150b, 150a is achieved. Once in a desired position and orientation, the position of the second body 234 within the cannula 230 is fixed.

[0226] The cannula 230 may be curved (e.g., I to J) or straight (K to M). The electrode body 234 that includes the active electrical contact 150b may be curved (e.g., K to M) or straight (I to J).

[0227] As illustrated in [Fig. 10], the active and return electrical contacts 150b, 150a may be combined with various combinations of electrical contact arc lengths. For example, configurations A, B, I, K, and L include electrical contacts in which the active and return electrical contacts 150b, 150a extend around the majority of the circumference of the electrode 120 (e.g., more than 180°, 270°, 360°). For example, configuration A illustrates an electrode 120 having active and return electrical contacts 150b, 150a extending around the entire circumference of the electrode 120. Configurations E through H, J, M provide exemplary electrodes 120 in which the return electrical contact 150a extends around less of the circumference of the electrode than the active electrical contact 150b. Similarly, the exemplary configurations illustrate the active and return electrical contacts 150b, 150a combined with various combinations of shapes, for example, configuration J where the return electrical contact 150a has a rectilinear shape and the active electrical contact 150b has a curvilinear shape. [Fig.10] also illustrates combined active and return electrical contacts 150b, 150a of different contact lengths and circumferences, e.g., configurations B and C provide an electrode where the return electrode 150a is shorter (along the longitudinal axis of the electrode 120) than the active electrode 150b. Configurations J and M provide an electrode where the return electrode 150a is longer than the active electrode 150b. Configurations I, K illustrate a probe where the return electrode 150a has a circumference greater than that of the active electrode 150b.

[0228] Figures 11A and 11B illustrate an exemplary connection between the electrode 120 and the wire (L) electrically coupling the electrode 120 to the generator 140. The connection may be facilitated by the design of the proximal end of the electrode 120 and / or an electrode connector 128 coupled to the proximal end of the electrode 120. As provided in Figure 6A, the electrode 120 and / or the electrode connector 128 may comprise a concentric design, such that a plurality of circumferentially shaped contacts are arranged as concentric surfaces superimposed around the major axis of the electrode 120.For example, as illustrated in Figure 6A, contact A is the outermost conductive surface, contact B is an inner conductive surface (facing toward the long axis of electrode 120), contact C is another inner conductive surface (facing away from the long axis of electrode 120), and contact D is the innermost conductive surface (facing toward the long axis of electrode 120). The concentric surfaces may each be electrically connected to unique components of electrode 120 (e.g., the active electrical contact (distal electrical contact 150a), the return electrical contact (proximal electrical contact 150b), and / or the temperature sensing element 210). The concentric surfaces may be separated by dielectric layers including, for example, electrically insulating materials and / or air provided between adjacent conductive surfaces.For example, a dielectric layer having a thickness of between 0.01 mils and 50 mils may be provided between adjacent concentric surfaces. The needle gauge may vary along the electrode shaft 120 or may be constant to accommodate . concentric designs. Additionally, the needle gauge can be selected to allow for the passage of light in addition to routing active electrical, return, and temperature sensing traces / circuits.

[0229] The wire (L) may include a compatible cable and / or connector for electrically coupling the electrode 120 and / or an electrode connector 128 to the generator 140. The cable / connector of the wire (L) includes concentric surfaces (e.g., A, B, C, D) of corresponding size and shape and configured to electrically mate with the corresponding concentric surfaces of the electrode 120 / connector 128 and provide low and consistent electrical connectivity between the generator 140 and the electrode 120.

[0230] The concentric surfaces may be designed to compress or expand when appropriate mechanical pressure is applied, thereby allowing a reliable and precise fit between the wire (L) and the electrode 120. For example, the concentric surfaces provided on the wire (L) and / or the electrode 120 / the connector 128 may include notches in some of the conductive surfaces or in the dielectric layers provided between the concentric surfaces. The notches allow for controlled expansion of the concentric surface while maintaining constant contact with the corresponding surface of the electrode 120 (or the wire (L)).

[0231] The concentric design of the wire (L) and / or the electrode may include a lumen to allow passage of fluid through and / or between the wire (L) and the electrode 120. For example, the probe connector 128 may include a lumen extending within the innermost concentric layer (and / or between other concentric layers) allowing attachment of a syringe or tubing to the connector 128 and injection of fluid through the innermost concentric layer or between other concentric layers.

[0232] Additionally, the concentric design may be adopted not only as a component of the connector, but also as a means of guiding the electrical circuits of the electrical contacts and temperature sensing elements from their end sites to the proximal end of the electrode 120 for connection to the generator 140. The concentric design, including the conductive surfaces and dielectric layers, may also be used along the electrode shank 120. Such a design lends itself to simple manufacturing processes and possibly to the use of the electrode shank 120 to provide the connection with the wire (L), i.e., without the use of a connector 128, as illustrated in FIG. 6B.

[0233] Additionally, the type and thickness of material for the dielectric layers located between the concentric surfaces, as well as the type and thickness of material for the conductive layers, may be selected to minimize capacitance and / or maximize the impedance between the conductive layers (e.g., to reduce shunting and noise) and maximize delivery of the therapeutic waveform to the tissue while minimizing the power requirements of the electrical generator).

[0234] One or more temperature sensors / thermal sensing elements 210 may be included on the electrode 120 to provide feedback regarding the electrode 120 and / or tissue temperature at specified locations. In one example, the one or more temperature sensors 210 are placed at locations that are expected to be sites of highest temperature, e.g., near locations of highest predicted current density, this includes, for example, sharp pointed ends, contact edges, discontinuities, or rapid spatial transitions between materials of different electrical conductivities. The choice of these temperature sensor placement locations may be determined based on modeling studies or in vitro or in vivo temperature measurements in tissues or in model media such as saline solutions, conductive gel formulations, or egg whites.The temperature sensor traces may be guided in a manner that reduces the level of electromagnetic interference introduced by the delivery of the waveform into the temperature sensing circuit.

[0235] In addition to the concentric arrangement, various other arrangements may be used to guide the active and return electrical contacts and thermal sensing elements from their end sites to the position where they connect to the wire cable (L) or generator 140, including, for example, guiding insulating wires, using dielectric layers with non-insulating wires, and printing electrical traces with electrically conductive ink, etc. In addition, the materials used to guide the active and return contacts and thermal sensing elements from their end sites to the position where they connect to the wire cable (L) or generator 140 may be carefully selected to allow reliable and efficient transmission of the electrical signals without contamination or bypass.It should also be noted that such approaches may be used in cases where multiple electrical contacts 150 or multiple thermal sensing elements 210 are used on a single electrode 120.

[0236] SIGNAL GENERATOR EXAMPLE

[0237] The electrical stimulation device 100 may include a signal generator 140 coupled to the electrode 120 and the controller 130. The signal generator 140 produces the stimulation waveform, including the stimulation waveform parameters described above. The signal generator 140 includes the software and hardware components necessary to produce the specified stimulation waveform(s) and to enable modulation of the stimulation waveforms. mulation by means of the controller 130. The signal generator 140 also includes the capability of delivering stimulation to the nerve structure via the electrode(s) 120 while electrically isolating the electrode 120 and the patient from grounded circuits and other ground connections, so that the patient is not grounded when the electrode(s) are introduced into the patient's body. This is accomplished, for example, via inductors or optical isolators. In addition, the signal generator 140 may include capacitors, inductors, resistors, and other passive circuit components near the output of the electrode 120 that provide charge balancing, reduce DC offset, or otherwise provide the desired regulation of the waveform parameters described above.Further, feedback monitoring circuitry may be integrated to collect information regarding the delivered waveform (such as current, voltage, power) and temperature (monitored, for example, via a temperature monitoring mechanism (e.g., a temperature sensor 210) at the electrode 120 or otherwise in the tissue). Parameters of the cooling mechanism such as the temperature of the fluid / gaseous cooling medium, the flow rate and pressure of the fluid / gas, the heat transfer rate of the electrode 120 and / or the surrounding tissue, etc. may also be collected.

[0238] EXAMPLE OF CONTROL AND POWER SUPPLY DEVICE

[0239] As generally described above, the controller 130 directs the operation of the stimulation device 100 / signal generator 140 to provide the electrical stimulation to the target neural structure by means of the electrode 120. The controller 130 / signal generator 140 is electrically coupled to a power source 180 which provides the electrical power to the stimulation device 100 / electrode 120. The power source 180 may include an isolated power supply, such that all instruments in the system may be powered by an isolated power supply 180 to protect them from ground faults and power spikes carried by the electrical circuit.The power source 180 may also include one or more batteries, used either for primary power or for backup power, which would allow the device to be operated without connection to the facility's electrical mains.

[0240] Specifically, the controller 130 directs the operation of the signal generator 140 to deliver an electrical stimulation signal to the target nerve structure. The controller 130 may have integrated memory to facilitate high-speed data capture, output control and processing, as well as independent waveform sampling rates and online analysis. These components of the controller enable the collection of feedback data necessary for understanding the waveform delivered via the electrode, as well as the parameters of the cooling mechanism and the thermal and electrical state of the tissue. This feedback allows adjustment of such treatment parameters to provide selective and reversible inhibition of pain.

[0241] As schematically illustrated in [Fig.l], the stimulation device may include one or more electrodes 120 connected by an electrical wire (L) to the controller 130 via the signal generator 140. The controller 130 may include control logic and software designed to deliver the desired electrical stimulation to a patient. The controller 130 may also process analog and digital data and record waveform data and digital information from the patient monitoring system 190 and may generate waveform outputs, analog outputs, and digital outputs simultaneously for real-time control of the electrical stimulation (real-time automatic control, or manual user control).For example, the controller 130 may adjust electrical stimulation in response to feedback received from temperature sensors coupled to the electrode 120 and / or the stimulation device 100. For example, the stimulation device 100 / electrode 120 may include a thermocouple to measure temperature at the contact surface of the stimulation device and / or the electrode contacts, as well as patient tissue adjacent to the contact surface of the electrode 120. The temperature sensors are coupled to the controller 130 and provide feedback regarding a temperature measured at the contact surface of the stimulation device 100 and / or the contact surface of the electrode 120 and / or at other locations in the tissue.The controller 130 or the user may then adjust a parameter of the electrical stimulation in response to the feedback, the parameters including, for example, a waveform, a wave frequency range, a wave amplitude range, an electric field strength generated at an electrode, a DC wave offset, a wave duty cycle (e.g., continuous delivery or intermittent delivery), a tissue temperature, a cooling mechanism parameter, and a treatment duration.Additional feedback signals that may be relayed or recorded by the controller or used for feedback control of the electrical signal include temperature, contact impedance, current, voltage and power of the electrical signal, other parameters of the electrical signal, information about the electric field in the tissue, blood flow, skin conductance, heart rate, muscle activity (such as electromyography) or other physiological signals.

[0242] Feedback control of electrical stimulation is desirable to avoid cause tissue damage, to adjust the modulation sphere of electrical stimulation within the target neural structure, and to adjust the modulation sphere of electrical stimulation to target small and large nerve structures and a variety of nerve structures such as peripheral nerves, cranial nerves, ganglia, autonomic nerves, plexuses, and the spinal cord. Feedback control of electrical stimulation is also desirable to allow temporal adjustment of the reversibility of pain perception inhibition, to adjust the selectivity of adequate pain inhibition, for example, with a single treatment.

[0243] Whether to adjust the electrical stimulation to selectively modulate nerve signal transmission via a selected type of nerve fiber and / or via a selected region of the nerve structure, the control and / or operation of the controller 130 may be adjusted as a function of a parameter of the electrical stimulation based on measured feedback of inhibition of nerve signal transmission (e.g., confirmation of no or limited nerve signal transmission from / via the target nerve) and / or measured feedback of temperature at the treatment site and / or patient feedback regarding pain perception.Confirmation of no or limited nerve signal transmission may be achieved using intraoperative monitoring techniques, such as, for example, recorded EMGs, direct nerve recordings that demonstrate a change in pain fiber response in latency and / or amplitude or burst area. The controller 130 and user interface are also used to adjust the parameters of the stimulation waveform and the properties of the electrode configurations and the cooling mechanism in response to feedback. For example, the controller 130 is configured to vary the duty cycle and / or stimulation envelope duration of the electrical stimulation in real time, during treatment, to maximize the voltage delivered to the treatment site without exceeding the temperature of the target tissue at the treatment site, i.e., a tissue-destructive temperature.Similarly, in some embodiments, the controller is configured to vary the duty cycle and / or stimulation waveform envelope duration of the electrical stimulation in real time to maximize the current delivered to the treatment site without exceeding the temperature of the target tissue at the treatment site, i.e., a tissue-destructive temperature. Providing an immediate temperature-sensitive feedback loop allows a therapeutic voltage (or current) to be delivered to the target nerve structure for the longest time possible without causing damage. By controlling the current, the user can more easily control the temperature of the tissue. and safety. Similarly, voltage control is correlated with treatment effectiveness.

[0244] Alternatively, a user may manually adjust the parameters of the stimulation waveform and the properties of the electrode configurations and the cooling mechanism in response to feedback provided via the user interface 170.

[0245] EXAMPLE OF USER INTERFACE

[0246] The stimulation device 100 may further include a user interface 170 for receiving user input and providing input to the user (e.g., a patient or healthcare professional). The user may assist in directing the operation of the stimulation device 100 including changes to the electrical signal. The user interface 170 may further include a display providing information to the user regarding the stimulation device 100. For example, the display may provide information regarding the status of the stimulation device 100, e.g., enabled / disabled, signal transmission mode, parameter date regarding the electrical signal, etc. The user interface 170 may be an integral part of the stimulation device 100.It is also contemplated that the user interface 170 may be incorporated into a remote device that is electrically coupled (wired or wireless) to the stimulation device. For example, the user interface 170 may be provided on an external tablet or phone. The user interface 170 may be used to allow the user to actively control the parameters of the electrical stimulation (in real time) in response to feedback from the control device 130.

[0247] The system may also include a patient monitoring system 190. The patient monitoring system 190 may be used in conjunction with the stimulation device and the user interface 170. The patient monitoring system 190 acquires, amplifies, and filters physiological signals and sends them to the controller 130 and / or the user interface 170 for feedback. The monitoring system may include a temperature sensor coupled to an external surface of the patient's skin to measure changes in body temperature at the patient's surface, a blood flow meter coupled to or inserted into the patient's skin, a skin conductance meter coupled to the patient's skin, a heart rate monitor for collecting electrocardiogram signals corresponding to the patient's heart rate, and a muscle activity monitor for collecting electromyography signals.A heart rate monitor may include separate electrocardiogram (ECG) electrodes coupled to an alternating current (AC) amplifier. A muscle activity monitor may include separate EMG electrodes coupled to an AC amplifier. Other types of transducers may also be used. As described, all signals . physiological signals obtained with the patient monitoring system pass through a signal amplifier / conditioner. The parameters of the electrical stimulation may be adjusted in response to feedback received on the patient monitoring system 190 by the controller 130 or the user. For example, at least one parameter of the electrical signal may be adjusted by the controller 130 in response to feedback received from the temperature sensor, an impedance meter, the blood flow meter, the skin conductance meter, the heart rate monitor, and the muscle activity monitor.Information regarding the stimulation waveform and parameters as well as the electrical and thermal properties of the tissue, electrode, and cooling mechanism may also be provided via the user interface 170 and used to adjust at least one parameter of the electrical stimulation or cooling mechanism or electrode configuration.The adjusted parameter of the electrical signal may include, for example, a waveform, a wave frequency range, a wave amplitude range, a wave envelope duration range (i.e., the period of time the stimulation energy is delivered (“on”), e.g., continuously delivered stimulation energy has a long envelope duration and pulsed stimulation energy has a short envelope), an electric field strength at the electrode, a DC wave offset, a wave duty cycle (e.g., continuous delivery, intermittent delivery), a tissue temperature, a parameter of the cooling mechanism, and a treatment duration. In addition, the configuration of the electrodes (e.g., bipolar, multipolar, unipolar, alternating, etc.) may also be adjusted in response to the feedback.

[0248] EXAMPLE OF PROCESS

[0249] The present invention relates to a method for selectively and reversibly modulating targeted nervous or non-nervous tissue of a nervous structure with a single application of electrical energy to inhibit the perception of pain by a patient. The method of practicing the present invention begins by positioning the patient in a comfortable position. A heart rate monitor (ECG), a muscle activity monitor (EMG), or any other monitor may be used to measure the patient's response to the electrical stimulation signal. The patient may be monitored for a period of time to determine the baseline condition before the application of the electrical stimulation signal.

[0250] Next, the targeted nerve structure can be identified and located. If the electrical signal is to be delivered transcutaneously, the targeted nerve structure can be located using a stimulation device such as a nerve locator (e.g., an Ambu® Ministim® nerve stimulator and locator), using the electrode 120. The nerve can also be located by passing weak stimulation energy signal levels through the stimulation device. A muscle contraction elicited by a stimulus in a distal muscle group with low stimulation amplitudes (single pulse) will indicate that the stimulation point is close enough to modulate nerve signal transmission.

[0251] The electrical stimulation device 100 is then positioned at the treatment site near the targeted nervous or non-nervous tissue of the nerve structure. The electrode(s) 120 may be placed near the nerve structure percutaneously or transnasally, or by open incision and implantation.

[0252] For example, the electrodes 120 may be positioned percutaneously adjacent to the neural structure through an opening in the patient's skin (S) (see, for example, [Fig. 5]). The (internal) electrodes 120 / leads (L) are attached to an external stimulation device / signal generator 140, or may be attached to a portable stimulation device. Placement of the electrodes 120 percutaneously may include penetrating the skin and navigating the electrode 120 and / or the lead (L) under imaging guidance (such as with ultrasound) to a location near the target neural structure. Additional positioning tools may be used, such as cannulas, guidewires, introducer needles, and trocars, to enable tissue navigation and possible placement of the electrode near the target neural structure.

[0253] Positioning the electrode 120 near the nerve structure may include delivering an initial electrical stimulation (i.e., low level electrical stimulation, <0.5 V) at the treatment site via the electrode 120 and measuring the voltage and / or current at the electrode 120. Based on the measured voltage and / or current, the position of the electrode 120 at the treatment site (near the target nerve structure) is adjusted. Further initial electrical stimulation signals are delivered at the treatment site and the position of the electrode 120 is adjusted, iteratively until the measured voltage and / or current corresponds to a threshold voltage and / or a threshold current indicating that the electrode 120 is positioned around the nerve at a location to deliver effective treatment.

[0254] When the electrical signal is delivered percutaneously, the method may further comprise positioning one or more return electrodes on the outer surface of the patient's skin. Each anode preferably has a skin-contacting surface such that the skin-contacting surface of the anode has at least the same area (or a larger area) as the contact surface of the stimulating electrode. One or more return electrodes may be placed on the skin at a distance from one or more stimulating electrodes sufficient to avoid shunting.

[0255] The method of practicing the present invention may further include the use of coupling means such as, for example, an electrically conductive liquid, gel, or paste that may be applied to the skin in the case of a return electrode or disposed in a sheath surrounding the electrode 120 or at the tip of the electrode 120 in the case of the percutaneously placed electrode 120 in order to maximize and direct the electrical field, deliver the therapeutic dose of stimulation energy to small and large nerves, and ensure reliable placement of the electrodes / nerves for optimal therapeutic effect. Alternatively and / or additionally, one or more skin moisturizers, humectants, exfoliants, or the like may be applied to the skin for the purpose of improving skin conductivity and / or reducing skin impedance.Examples of conductive pastes include Ten20™ conductive paste from Weaver and Company, Aurora, Colorado, and ELEFIX conductive paste from Nihon Kohden with offices in Foothill Ranch, California. Examples of conductive gels include Spectra 360 electrode gel from Parker Laboratories, Inc., Fairfield, New Jersey, or Electro-gel from Electro-Cap International, Inc., Eaton, Ohio. An example of an exfoliant that can be used to prepare the skin prior to the application of transcutaneous electrodes is Nuprep skin preparation gel from Weaver and Company, Aurora, Colorado.

[0256] In another example, the electrodes may be implanted in the patient adjacent to the treatment site and proximate the target neural structure. The electrodes and the stimulation device may be implanted at or proximate the target neural structure. In another example, the electrodes may be implanted at the treatment site, with the wires extending through the patient's skin to the stimulation device. It is also contemplated that the electrodes may be implanted at the treatment site and may be wirelessly activated through the patient's skin. It is also contemplated that a wireless receiver module may be implanted and used to receive wireless input from the controller 130 and then communicate with the electrode via conductive wires.

[0257] Another example is placement of the electrode 120 (e.g., [Fig. 3F]) in a nasal turbinate via a transnasal approach for transmucosal delivery of the electrical signal to the gasserian ganglion and / or the sphenopalatine ganglion (SPG). For example, the electrode 120 and wire may be inserted into the patient's nose and placed in a nasal turbinate and held securely during delivery of the electrical signal (see, e.g., Figures 9A and 9B). A method may be used in which the patient's sneeze reflex is suppressed, e.g., by using a chemical block or an electrical nerve block or by intentionally evoking a sneeze reflex and then placing the wire and electrode immediately after the sneeze before the patient can generate a second sneeze reflex. The reflex The initial intentional sneeze may be triggered by the wire and / or electrode or by a separate probe inserted into the nose. It is also contemplated that the electrode 120 may be positioned adjacent to the gasserian ganglion and / or the sphenopalatine ganglion (SPG) by a percutaneous approach. Whether by a transnasal or percutaneous approach, the position of the SPG may be initially localized using, for example, magnetic resonance imaging (MRI), fluoroscopy, and ultrasound imaging.

[0258] Once the electrodes 120 are placed, conventional electrical stimulation may be delivered through the electrodes 120 to ensure sufficient proximity to the tissue / nerve, and impedance measurements may be collected and used in a similar manner. The stimulation device may then be programmed to optimize electrode contact selection, return electrode selection, and stimulation parameters, as discussed above. It is contemplated that selecting optimal stimulation parameters may include delivering different candidate waveforms with different parameter configurations until a suitable result is achieved.It is further contemplated that selecting the optimal electrode contact 150 configurations and return electrode configurations may include delivering electrical signals through different electrode contact 150 and return electrode configurations until a suitable result is achieved. These optimizations may be performed manually by the user or may be delivered by the closed-loop controller as part of an iterative algorithmic search or a pre-programmed search. If desired, a chemical nerve blocking agent may also be administered through the electrode wire prior to delivering the electrical signal. The chemical nerve blocking may help to attenuate the apparent response and improve patient comfort.

[0259] The electrical stimulation signal may then be delivered to the treatment site proximate the targeted nerve structure via the one or more electrodes using one or more of the stimulation parameters described above. The controller 130, receiving a supply of electrical energy from a power source 180, may direct operation of the stimulation device to provide an electrical signal sufficient to selectively modulate the targeted nervous or non-nervous tissue inhibiting the patient's perception of pain while preserving other sensory and motor functions and proprioception. The user may also control the parameters of the electrical signal in real time in response to feedback provided via the controller 130 to the user interface 170.A single application of the electrical signal at the treatment site can selectively modulate the targeted nervous or non-nervous tissue and subsequently inhibit pain perception for a period of about 1 day to about 30 days.

[0260] Where the electrode comprises at least two electrodes that operate independently, it is contemplated that a first electrical stimulation signal may be delivered via the first electrode and a second electrical stimulation signal via the second electrode. The first and second electrical stimulation signals may be delivered intermittently, with the first electrical stimulation alternating with respect to the second electrical stimulation. In this configuration, the activation cycle of the first electrical stimulation occurs during a shutdown cycle of the second electrical stimulation. Similarly, the activation cycle of the second electrical stimulation occurs during a shutdown cycle of the first electrical stimulation.

[0261] The patient's perception of pain is inhibited because the application of the electrical signal at the treatment site selectively modulates the targeted nervous or non-nervous tissue modulating the transmission of the nerve signal by the nerve fibers responsible for pain transmission. Meanwhile, the transmission of the nerve signal by the nerve fibers responsible for other sensory and motor functions and proprioception is preserved. The preserved "other" sensory functions include, for example, touch, vision, hearing, taste, smell, and balance. The application of the electrical signal may also inhibit and / or disrupt the transmission of the nerve signal by the nerve fibers responsible for transmitting signals related to thermoreception, autonomic activity, and visceral function.

[0262] In its simplest form, the method may rely on patient feedback regarding their perception of pain after delivery of the nerve-blocking stimulation signal to assess the effectiveness of the temporary and selective nerve modulation. In some examples, patient sensations, such as heartbeat, tingling, heaviness, and / or deep pressure, experienced during stimulation may be used to direct various stimulation parameters, including voltage, current, stimulation impedance, and treatment duration (duty cycle and duration of stimulation; duration of treatment and end of treatment; delivery (duration of "on" stimulation).

[0263] Alternatively and / or additionally, the method may rely on feedback collected by a recording electrode, such as an electrocardiogram, galvanic skin response, blood flow meter, skin or body temperature, and / or electromyogram signals to assess the effectiveness of the temporary and selective nerve modulation, since the stimulation may occur before, during, or immediately after surgery, when the patient is unable to provide feedback.

[0264] The target nerve structure may include a peripheral nerve (large or small), a cranial nerve, a ganglion, an autonomic nerve, a plexus, and the spinal cord. Target neural structures may include a mixture of motor, sensory, and / or autonomic neurons, or may include only one type of neural activity (e.g., motor only, sensory only, autonomic only). Target ganglia may include dorsal root ganglia, sympathetic ganglia, parasympathetic ganglia, a sphenopalatine ganglion, a gasserian ganglion, a plexus, and / or the spinal cord.In one example, the target nerve structure comprises a large peripheral nerve (greater than about 2.5 mm, for example) and the electrodes deliver an electrical signal to the nerve that selectively and reversibly inhibits nerve signal activity associated with pain for a period of days to weeks, with preservation of nerve signaling associated with motor function, non-painful sensation, and proprioception. For example, the electrodes 120 may deliver an electrical signal that selectively and reversibly inhibits nerve signal activity in smaller diameter nerve fibers associated with sensory function (pain) for a period of days to weeks, with minimal or no change in the functionality of the larger myelinated fibers associated with motor function, non-painful sensation, and proprioception.In one example, application of the electrical signal to the nervous and non-nervous tissues of the targeted nerve structure inhibits and / or disrupts nerve signal transmission through at least one of a myelinated Aδ fiber and / or an unmyelinated C fiber provided in the nerve, wherein the electrical signal preserves nerve signal transmission through at least one of the Aδ and Aδ fibers and / or motor fibers. In another example, various parameters of the electrical signal may be adjusted to selectively inhibit at least one of the myelinated Aδ fibers or the unmyelinated C fibers, e.g., to inhibit nerve signal transmission through the myelinated Aδ fibers while preserving nerve signal transmission through the unmyelinated C fibers, and vice versa.In another example, various electrical signal parameters can be adjusted to differentially inhibit the nerve signal transmission / function of myelinated Aδ fibers, such that myelinated Aδ fibers have a higher percentage of inhibited fibers than unmyelinated C fibers. Similarly, various electrical signal parameters can be adjusted to differentially inhibit the nerve signal transmission / function of unmyelinated C fibers, such that unmyelinated C fibers have a higher percentage of inhibited fibers than myelinated Aδ fibers.

[0265] In another example, application of the electrical signal to the nervous and non-nervous tissues of the targeted nervous structure modulates the function of the nervous and non-nervous tissues so as to produce downstream or secondary effects resulting in the inhibition of pain, while preserving motor, non-painful sensory, and pro-prioceptive activity. For example, various parameters of the electrical signal may be adjusted to selectively modulate function resulting in reduced pain from activity in myelinated Aδ fibers and / or unmyelinated C fibers, while preserving motor, non-painful sensory, and pro-prioceptive function, such as that mediated by Aδ and Aδ fibers, and / or motor fibers. In another example, various parameters of the electrical signal may be adjusted to selectively modulate function resulting in reduced pain from activity in myelinated Aδ fibers or unmyelinated C fibers, e.g., inhibiting pain from activity in myelinated Aδ fibers while preserving pain from activity in unmyelinated C fibers, and vice versa.In another example, various parameters of the electrical signal can be adjusted to differentially modulate the function resulting in reduced pain from activity in myelinated Aδ fibers, such that pain from activity in myelinated Aδ fibers exhibits greater inhibition than pain from activity in unmyelinated C fibers. Similarly, various parameters of the electrical signal can be adjusted to differentially modulate the function resulting in reduced pain from activity in unmyelinated C fibers, such that pain from activity in unmyelinated C fibers exhibits greater inhibition than pain from activity in myelinated Aδ fibers.

[0266] In another example, certain parameters of the electrical signal may be adjusted to preferentially modulate nerve signal transmission / function in a desired region of the nerve structure. Generally, the desired region is the portion of the nerve structure comprising the sensory components responsible for transmitting the sensation of pain. For example, with respect to the femoral nerve, the topography of the femoral nerve indicates that portions of sensory components innervating the knee are collected together in one region of the nerve's cross-section. Accordingly, it is contemplated that the electrical signal may be adjusted to preferentially modulate nerve signal transmission through the portion of the nerve's cross-section corresponding to those target sensory components.

[0267] The various modifiable parameters of the electrical signal include, for example, waveform, frequency, amplitude, waveform envelope duration, intensity, electric field strength, waveform offset (DC offset), continuous delivery, and / or intermittent delivery across the electrode 120. For example, the controller 130 adjusts the duty cycle and / or waveform envelope duration in real time to maximize the voltage delivered to the treatment site, without exceeding a temperature of target tissue at the treatment site, for example, by modulating the stimulation duty cycle and / or the stimulation envelope to maximize the voltage delivered to the treatment site in real time while ensuring that the tissue present at the treatment site does not exceed a tissue-destructive temperature. Similarly, in some embodiments, the controller 130 adjusts the duty cycle and / or the waveform envelope duration in real time to maximize the current delivered to the treatment site, without exceeding the target tissue temperature at the treatment site, for example, by modulating the stimulation duty cycle and / or the stimulation envelope to maximize the current without exceeding a tissue-destructive temperature.

[0268] In another example, the stimulation amplitude of the electrical stimulation may be gradually increased to a plateau. The gradual increase in electrical stimulation may eliminate and / or reduce the magnitude of sensations experienced by the patient upon delivery of the electrical stimulation (e.g., tingling sensation felt in the receptive field of the nerve when the stimulation energy is continuous; intermittent tingling sensations felt when the stimulation energy is delivered in pulses).

[0269] The disclosed method encompasses inhibiting pain perception associated with acute pain (including operative pain, post-operative pain, traumatic pain), neuropathic pain, chronic pain, and head and facial pain. When the pain is acute pain, the method of selectively and reversibly modulating targeted nervous or non-nervous tissue to inhibit pain perception may include applying the electrical signal immediately prior to the surgical procedure. The electrical signal may also be applied intraoperatively and / or immediately following a surgical procedure to inhibit pain perception associated with the surgical procedure and recovery. The electrical signal may also be applied hours and / or days prior to a procedure. For example, the electrical signal may be applied at least 24 hours prior to a surgical procedure.Delivering the electrical signal before an intervention, such as a surgical procedure, helps reduce patient pain and discomfort while preparing the patient for the procedure. Delivering the electrical signal before an intervention can also be configured to allow the maximum pain relief effect to occur at the time of the intervention. It is also contemplated to target multiple nerve structures to allow more complete coverage of the target area. For example, when the pain is acute post-operative pain occurring after a knee replacement procedure (including a total knee replacement procedure), electrical stimulation can be applied to the femoral nerve, sciatic nerve, ob . turator and lateral cutaneous nerve and nerve branches, or a combination thereof. In another example, when the pain is shoulder pain, electrical stimulation may be applied to the brachial plexus, axillary nerve, suprascapular nerve, and lateral pectoral nerve, or a combination thereof. When the pain is associated with a medical procedure and / or trauma to the arm and / or hand, electrical stimulation may be applied individually to the medial, ulnar, and radial nerves and / or the brachial plexus. When the pain is associated with a medical procedure and / or trauma to the ankle and / or foot, electrical stimulation may be applied to the tibial, peroneal / sural, and saphenous nerves, or a combination thereof.When pain is associated with hip arthroplasty, electrical stimulation may be applied to the femoral, sciatic, or obturator nerve (e.g., the common obturator nerve before it branches into the anterior and posterior nerves) and / or plexus, or a combination of these. When pain is associated with anterior cruciate ligament (ACL) repair, electrical stimulation may be applied to the femoral or sciatic nerve, or a combination of these.

[0270] Where the pain is neuropathic pain or chronic pain, the method of modulating the nervous or non-nervous tissue of the target nervous structure may include the user (such as a physician or patient) applying the electrical signal as part of a predefined schedule for preventative care and / or as needed by the patient to provide an on-demand bolus of therapeutic treatment / pain relief.

[0271] The method of selectively and reversibly modulating targeted nervous and non-nervous tissues to inhibit pain perception may also include measuring, at a temperature sensor 210, the temperature of the contact surface of the stimulation device 100 (e.g., the contact surface of the electrode 120) and / or the temperature of the patient's tissue adjacent to the contact surface of the stimulation device during delivery of the electrical signal. Feedback regarding the measured temperature is sent to the stimulation device.If the feedback indicates that the temperature of the contact surface of the stimulation device is above a threshold temperature of the device and / or the temperature of the patient's tissue is above a threshold temperature of the tissue, the stimulation device / control device or the user may adjust the operation of the stimulation device and the parameters of the electrical signal and / or a cooling mechanism to produce a cooling effect and reduce the temperature at the contact surface and the tissue. Reducing the temperature of the contact surface and / or the patient's tissue prevents damage to the patient's tissue. In some examples, the system may include a cooling mechanism. cooling coupled and / or integrated with the stimulation device 100 and / or the electrodes 120. If the feedback indicates that the temperature of the contact surface of the stimulation device 100 is above a threshold temperature of the device and / or if the temperature of the patient's tissue is above a threshold temperature of the tissue, the stimulation device 100 / control device 130 and / or the user can activate and control the operation of the cooling mechanism to cool the contact surface of the stimulation device 100 / of the electrode 120, the cooling of the contact surface avoiding damage to the patient's tissue when the electrical signal is delivered by maintaining the temperatures of the patient's tissue below a threshold temperature of the tissue.Similarly, the stimulation device 100 / control device 130 and / or the user may activate and control the operation of the cooling mechanism to maintain the temperature of the contact surface of the stimulation device 100 / electrode 120 below a threshold temperature in response to feedback regarding the measured temperature received from the temperature sensor 210.

[0272] Once the electrical signal has been delivered and pain perception has been inhibited while preserving other sensory and motor functions, and proprioception, the percutaneous and / or transcutaneous electrodes 120 may be removed. While the implanted electrodes 120 (if any) may remain inside the body for further use and continued treatment. Example 1

[0273] In this example, able-bodied subjects were recruited from the community and consented to the study using IRB-approved consent forms. High-dose opioid users were excluded from the study. Two types of sensory assessments were performed at different times on each subject: 1) a mechanical vibration test to assess the subject's sensitivity to a non-painful touch sensation, and 2) a pain-eliciting electrical stimulation test to assess the subject's sensitivity to elicited pain. At the beginning of the first session, assessments of the mechanical vibration test and the pain-eliciting electrical stimulation were performed on each leg. These were referred to as baseline assessments. The subject then received treatment using the electrical stimulation waveform via an electrode placed on the left leg percutaneously.After treatment, mechanical and vibration testing was again assessed on each leg. Subjects returned at subsequent visits for mechanical vibration and electrical stimulation testing eliciting pain.

[0274] Mechanical vibration test: Subjects wore surgical scrubs and were seated in a comfortable chair. The right leg was fixed in a straight position to a support with foam padding to limit movement. A The vibration device was placed in contact with the skin within the distribution of the saphenous nerve. Vibration tests were then performed in which a series of two periods were applied to the subject, one including vibration via the vibration device and the other not including vibration. For each test, the choice of the period during which the vibration was triggered was determined randomly and the subject was asked to verbally indicate which period they thought the vibration had been delivered. If the subject chose the correct period, a new test was performed until the correct choice was made for three successive tests, after which the vibration amplitude was reduced for the next test. If the subject chose the incorrect period, the next test was performed with a higher stimulation amplitude.In this way, the threshold amplitude was determined based on the combined performance of 3 sets of 50 tests on each leg. The threshold amplitude was identified for each leg in each session.

[0275] Electrical stimulation test eliciting pain: Electrical stimulation was delivered via sticky surface electrodes placed on the saphenous nerve near the medial malleolus. Stimulation duration was 1 ms for single pulses. Stimulation amplitude was gradually increased until the subject first perceived a sensation. Stimulation was then delivered in a train of 9 pulses at 500 Hz and the stimulation amplitude was gradually increased until the subject perceived a transition from non-painful to painful sensation. Pain threshold was identified via ascending and descending limit tests and the average pain threshold for that session was documented. This threshold was identified for each leg in each session.

[0276] Electrical Stimulation Treatment: The electrical stimulation treatment was administered as a single treatment to each subject on the left leg only. After the baseline mechanical vibration test and the baseline pain-eliciting electrical stimulation test, the subject was prepared for administration of the electrical stimulation treatment.

[0277] The subject was positioned supine on a procedure table and the skin was prepared at a site over the saphenous nerve several centimeters distal and medial to the tibial tuberosity. A surface return electrode was placed on the contralateral leg over the gastrocnemius muscles. Ultrasound was used to identify the saphenous nerve and a radiofrequency probe (22 gauge, 4 mm exposed tip) was inserted through the skin. The position of the active tip of the radiofrequency probe was manipulated while stimulation (1 ms duration, 2 Hz) was delivered at progressively lower amplitudes. Manipulation of the probe position was performed until a threshold was reached sensory less than 0.2 V.

[0278] The electrical stimulation treatment was then delivered to the subject at 2 Hz, 20 ms, for 240 s. The stimulation amplitude was adjusted in real time to maintain a probe tip temperature of 42°C. After stimulation was completed, the probe was removed and the subject underwent a further mechanical vibration test and a pain-eliciting electrical stimulation test, referred to as Visit 0.

[0279] Subjects returned for follow-up assessment at subsequent visits. Vibration thresholds were plotted over time to assess the effect of electrical stimulation treatment on tactile sensation, such as sensation transmitted via large-diameter myelinated fibers. Pain thresholds were normalized to baseline and plotted over time to assess the effect of electrical stimulation treatment on painful sensations, such as sensations transmitted via small-diameter fibers.

[0280] [Fig. 10] shows the time-normalized pain thresholds for five subjects who received electrical stimulation treatments lasting 240 s. The green line shows the mean response for local analgesics such as lidocaine or bupivacaine, which provide analgesia for a period of less than one day. An increase in pain thresholds was evident for all subjects, indicating a decrease in pain sensitivity. Return to baseline was evident seven days after the intervention.

[0281] [Fig. 11] shows mechanical vibration thresholds over time for the same five subjects (electrical stimulation treatments lasting 240 s). No systematic changes in mechanical vibration thresholds were evident, suggesting treatment selectivity for pain perception. Furthermore, results of a clinical examination indicated no sensory deficit in the treated leg.

[0282] These results suggest that electrical stimulation treatment selectively and reversibly increases the pain perception threshold via a treated nerve with complete reversibility within 7 days following treatment.

[0283] EXAMPLE OF COMPUTER SYSTEM

[0284] Although the methods and systems have been described in connection with preferred embodiments and specific examples, it is not intended that the scope be limited to the particular embodiments indicated, as the embodiments described herein are intended to be in all respects more illustrative than restrictive.

[0285] As used herein, the term "computing device" may include a plurality of computers. The computers may include one or more hardware components such as, for example, a processor, a random access memory (RAM) module, a read only memory (ROM) module, a storage memory, a database, one or more multiple input / output (I / O) devices and an interface. Alternatively, and / or additionally, the control device may include one or more software components such as, for example, a computer-readable medium comprising computer-executable instructions for performing a method associated with the exemplary embodiments. It is contemplated that one or more of the hardware components listed above may be implemented using software. For example, the storage may include a software partition associated with one or more other hardware components. It is understood that the components listed above are exemplary only and are not intended to be limiting.

[0286] The processor may include one or more processors, each configured to execute instructions and process data to perform one or more functions associated with a computer for indexing images. The processor may be communicatively coupled to RAM, ROM, storage, database, I / O devices, and the interface. The processor may be configured to execute sequences of computer program instructions to perform various methods. The computer program instructions may be loaded into RAM for execution by the processor. As used herein, processor refers to a physical hardware device that executes coded instructions to perform functions on inputs and create outputs.

[0287] A processor may be a microcontroller, a microprocessor, or a logic circuit such as an ASIC (Application Specific Integrated Circuit), a CPLD (Complex Programmable Logic Device), an FPGA (Field Programmable Gate Array), or any other programmable logic integrated circuit. In some embodiments, a processor is configured to execute an instruction stored in a memory of the device.

[0288] The RAM and ROM may each include one or more devices for storing information associated with operation of the processor. For example, a ROM may include a memory device configured to access and store information associated with the control device, including information for identifying, initializing, and monitoring operation of one or more components and subsystems. The RAM may include a memory device for storing data associated with one or more operations of the processor. For example, a ROM may load instructions into the RAM for execution by the processor.

[0289] The storage may include any type of mass storage device configured to store information that the processor may need to execute processes compatible with the disclosed embodiments. For example, the storage may include one or more magnetic and / or optical disks, such as hard disks, CD-ROMs, DVD-ROMs, or any other type of media device. mass.

[0290] The database may include one or more software and / or hardware components that cooperate to store, organize, sort, filter, and / or organize data used by the controller and / or processor. For example, a database may store hardware and / or software configuration data associated with hardware devices and input-output controllers, as described herein. It is contemplated that the database may store additional and / or different information than that listed above.

[0291] The I / O devices may include one or more components configured to communicate information to a user associated with the control device. For example, the I / O devices may include a console with an integrated keyboard and mouse to allow a user to manage an image database, update associations, and access digital content. The I / O devices may also include a display including a graphical user interface (GUI) for outputting information to a monitor. The I / O devices may also include peripherals such as, for example, a printer for printing information associated with the control device, a user-accessible disk drive (e.g., a USB port, a floppy disk, a CD-ROM or DVD-ROM drive, etc.) to enable a user to input data stored on a portable media device, microphone, speaker system, or other suitable interface device.

[0292] The interface may include one or more components configured to transmit and receive data via a communications network, such as the Internet, a local area network, a peer-to-peer workstation network, a direct link network, a wireless network, or any other suitable communications platform. For example, the interface may include one or more modulators, demodulators, multiplexers, demultiplexers, network communication devices, wireless devices, antennas, modems, and any other type of device configured to enable data communication via a communications network.

[0293] Unless otherwise expressly stated, it is in no way intended that any of the methods set forth herein be construed as requiring that its steps be performed in any specific order. Therefore, if a method claim does not actually recite an order to be followed or if the claims or description do not otherwise specify that the steps are to be limited to a specific order, it is in no way intended that an order can be inferred in any respect. This applies to any possible non-express basis for interpretation, including: questions of logic concerning the arrangement of steps or operational flow; a simple meaning derived from grammatical organization or punctuation; the number or type of embodiments described in the description.

[0294] Throughout this application, various publications may be referenced in order to more fully describe the state of the art to which the methods and systems relate.

[0295] It will be apparent to those skilled in the art that various modifications and variations may be made without departing from the scope and spirit of the invention. Other embodiments will become apparent to those skilled in the art from consideration of the specification and practice disclosed herein. It is intended that the description and examples be considered by way of example only, with only the following claims indicating the true scope and spirit of the invention.

Claims

Claims

1. A system for selectively and reversibly modulating targeted nervous or non-nervous tissue of a nervous system structure, the system comprising: an electrical stimulation device comprising one or more electrodes that are operable to deliver electrical stimulation at a treatment site located proximate to the targeted nervous or non-nervous tissue of the nervous system structure; and a controller configured to connect to one or more electrodes of the electrical stimulation device and to a power source for providing electrical energy to the one or more electrodes,the controller being configured to direct operation of the electrical stimulation device and apply the electrical stimulation at the treatment site via the one or more electrodes to provide selective modulation of the targeted nervous or non-nervous tissue inhibiting pain and preserving other motor and sensory functions, as well as proprioception, wherein the controller is adjustable to apply the electrical stimulation to differentially inhibit the function of myelinated Aδ fibers or nerve fibers responsible for a sharp / shooting pain sensation such that the myelinated Aδ fibers and / or the nerve fibers responsible for a sharp / shooting pain sensation have a higher percentage of inhibited fibers than the unmyelinated C fibers.,

2. The system of claim 1, wherein the one or more electrodes are of suitable size and shape to be positioned adjacent to the nervous system structure comprising at least one of a peripheral nerve, a cranial nerve, a ganglion and an autonomic nerve, a plexus and the spinal cord.

3. A system according to any one of claims 1 or 2, wherein at least one of the electrode(s) has a size and shape and contact surface configuration that is sufficient to deliver electrical stimulation to the nerve or ganglion and wherein the controller is configured to generate a suitable waveform forming the electrical stimulation to modulate the targeted nervous or non-nervous tissue of the nervous system structure.

4. A system according to any one of claims 1 to 3, wherein the The controller is configured to direct operation of the electrical stimulation device to vary the electrical stimulation based on measured feedback selected from the group consisting of: measured inhibition of nerve signal transmission, measured temperature, patient input, feedback corresponding to at least one of the adjustable parameters, a treatment setting associated with a recovery time, a contact impedance of the electrode, an electric field generated in the tissue, a physiological response of the patient, and a combination thereof.

5. Cl. The system of any one of claims 1 to 4, wherein the controller is configured to direct operation of the electrical stimulation device to vary at least one parameter of the electrical stimulation to modulate nerve signal transmission via i) at least one of myelinated Aδ fibers and / or unmyelinated C fibers or ii) a large nerve or ganglion or neural structure, wherein the at least one parameter is selected from the group consisting of a waveform, a wave frequency, a wave amplitude, a wave envelope duration, an electric field strength generated at the at least one electrode, a DC wave offset, a wave duty cycle, a tissue temperature, a cooling mechanism parameter, and a treatment duration.

6. The system of any one of claims 1 to 5, wherein the controller is configured to direct operation of the electrical stimulation device to deliver electrical stimulation at the treatment site having a frequency selected from a frequency range of 100 kHz to 1 MHz, 200 kHz to 800 kHz, 400 kHz to 600 kHz, and 450 kHz to 550 kHz, wherein the electrical stimulation delivered at the treatment site comprises at least one of: an amplitude range of between 5 mA and 1.25 A, an amplitude range of between 10 V and 500 V, a power range of between 0.1 W and 1250 W, and an electric field strength at the target site and / or the electrode(s) of between 20 kV / m and 2000 kV / m.

7. A system according to any one of claims 1 to 6, wherein the or the electrodes are sized and / or shaped to maximize and direct the electric field toward the structure of the nervous system, wherein the one or more electrodes comprise at least two electrical contacts, wherein each of the electrical contacts has a length of between 1 and 50 mm, preferably a length of between 2 mm and 20 mm, a length of between 2 mm and 15 mm, or 5 mm and 10 mm.

8. The system of any one of claims 1 to 7, further comprising: a temperature sensor coupled to the stimulation device for measuring a temperature of at least one of i) a contact surface of the stimulation device and ii) patient tissue adjacent to the contact surface or the electrode, wherein the temperature sensor is coupled to the controller and provides thermal feedback regarding a measured temperature, and a cooling mechanism configured to provide a cooling effect at the treatment site to prevent damage to the treatment site, wherein the controller is adjustable to vary at least one parameter of the electrical stimulation in response to thermal feedback received from the temperature sensor.

9. 9. The system of any one of claims 1 to 8, wherein the controller is adjustable to apply the electrical stimulation to differentially inhibit the function of unmyelinated C-fibers or nerve fibers responsible for a dull / hyperacute pain sensation such that the unmyelinated C-fibers and / or nerve fibers responsible for a dull / hyperacute pain sensation have a higher percentage of inhibited fibers than the myelinated Aδ fibers.

10. 10. The system of any one of claims 1 to 9, wherein the electrode(s) comprises an electrode assembly in the form of an elongate body, the distal end of the elongate body comprising a curvature such that a distal end portion of the elongate body extends at an angle relative to a longitudinal axis of the elongate body, the angle of the distal end portion relative to the longitudinal axis of the elongate body being between 0 and 50 degrees, preferably between 5 and 15 degrees.

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