Treating pain with photobiomodulation applied transcutaneously

Abstract

Photobiomodulation (PBM) can be transcutaneously applied using a PBM delivery system including an optical emitter to deliver PBM through a location on the patient's skin to one or more target nerves and a shield to extend outward around a portion of the optical emitter and block escape excess light. The system can also include a target locating system that can test various locations on the skin for identifying parameters of the one or more target nerves and / or locate the one or more target nerves. For instance, the system can include one or more electrodes for determining a depth of the one or more target nerves and / or imaging device(s) for locating where to apply the PBM on the skin. Parameters for the PBM can be determined by a controller of the system based on at least the location and / or depth of the one or more target nerves.

Description

NONPROVISIONAL APPLICATIONTREATING PAIN WITH PHOTOBIOMODULATION APPLIED TRANSCUTANEOUSLYCross-Reference to Related Applications

[0001] This application claims the benefit of U.S. Provisional Application No.63 / 572,494, filed April 1 , 2024, entitled “TREATING PAIN WITHPHOTOBIOMODULATION APPLIED TRANSCUTANEOUSLY”, and U.S. ProvisionalApplication No. 63 / 624,870, filed January 25, 2024, entitled “SYSTEMS AND METHODS TO SILENCE SMALL FIBERS TRANSCUTANEOUSLY”. These provisional applications are hereby incorporated by reference in its entirety for all purposes.Government Funding

[0002] This invention was made with government support under NS121372 awarded by the National Institutes of Health. The government has certain rights in the invention.Technical Field

[0003] This disclosure relates generally to treatment of neurological conditions (e.g., pain) and more specifically to systems and methods that transcutaneously apply one or more doses of photobiomodulation (PBM) to one or more target nerves under a skin of a patient to treat one or more neurological conditions (e.g., pain).Background

[0004] Photobiomodulation (PBM) can be used to treat acute and / or chronic pain when applied to a nerve. The PBM can target small fibers within the nerve that transmit nociceptive signals conveying pain information to the brain. Blocking these small fibers for an extended period of time can prevent or decrease the severity of pain.Traditionally, transcutaneous PBM delivery has not been used to target inhibition of specific nerves because: (1 ) the large majority of PBM is done to stimulate (and not inhibit nerves), (2) inhibiting small fibers of nerve takes more light than causing stimulatory effects, (3) PBM generally has difficulties in providing adequate amounts of light through the skin, and (4) many nerves are too deep to reasonably target throughthe skin. One alternative method has been to deliver PBM from under the skin (e.g., requiring surgery or otherwise piercing the skin). However, in many cases it is desirable to deliver PBM without requiring surgery and / or otherwise piercing the skin. Yet, there are multiple, unique challenges to delivering PBM transcutaneously in a manner that is both safe and efficacious for a given patient. Challenges include determining a location on the skin to deliver the PBM relative to the one or more target nerves, the distance between the PBM delivery device and the one or more target nerves, and the effect of a patient’s skin tone on the PBM dosage. Other safety challenges for transcutaneous light applications include shielding the user and the patient from excess light of the PBM and managing repeated doses, and managing heat created by generation of light or absorption of light. No current device is capable of meeting these challenges, so an optimized transcutaneous PBM therapy has not been available to patients.Summary

[0005] Described herein are systems and methods that can provide an optimized transcutaneous photobiomodulation (PBM) therapy to treat one or more neurological conditions (e.g., pain) of a patient. The systems and methods can include unique shielding elements and / or sensing mechanisms connected to a controller to determine connection to the skin and / or parameters for safe and efficacious transcutaneous PBM delivery (and, in some instances, electrical stimulation delivery).

[0006] In an aspect, the present disclosure can include a system for delivery PBM through a skin of a patient. The system can include an optical emitter and a shield. The optical emitter can be configured to deliver a dose of PBM with parameters for the dose of PBM through a location on the patient’s skin to one or more target nerves. The shield can be configured to extend outward around at least a portion of the optical emitter and to block escape of at least the wavelength of the dose of PBM. In some instances, the system can also include a target locating system comprised of a querying device configured to test various locations for at least one identifying parameters indicative of at least one target nerve and a recording device configured to locate the one or more target nerves under skin of a patient.

[0007] In another aspect, the present disclosure can include a wearable patch configured to be worn on skin of a patient. The wearable patch can include at least askin-side layer and a layer configured to block escape of at least the wavelength of a dose of PBM applied by the wearable patch. The skin-side layer can include an adhesive portion configured to attach to the skin of the patient. The skin-side layer can also include at least one opening configured to facilitate transmission of a dose of PBM having dose parameters through the skin of the patient to at least one nerve to modify conduction in at least one sensory fiber related to pain, inflammation, arthritis, symptoms of arthritis, and / or heat hypersensitivity. The wearable patch can also include at least one optical emitter positioned relative to the opening such that the dose of PBM travels out the opening towards the skin of the patient. In some instances, the wearable patch can further include one or more electrodes configured to stimulate and / or record signal(s) from the one or more target nerves.

[0008] In a further aspect, the present disclosure can include a method for determining a dosage of PBM for transcutaneous application to one or more target nerves. A system comprising a processor, can identify a location of one or more target nerves under skin of a patient based on at least one identifying parameter provided by a target locating system and / or input according to instructions from the patient. The target locating system can be configured to record the at least one identifying parameter related to the one or more target nerves under the skin of the patient. The one or more target nerves can each comprise at least one sensory fiber related to pain, inflammation, arthritis, symptoms of arthritis, and / or heat hypersensitivity. The system can estimate a depth of the one or more target nerves under the skin based on the at least one identifying parameter and configure dose parameters for a dose of PBM to be applied through the skin to modify conduction in the at least one sensory fiber related to pain based on the location and the depth of the one or more target nerves. The system can then send the dose of PBM to a PBM delivery system configured to deliver the dose of PBM with the dose parameters through the patient’s skin to the one or more target nerves.

[0009] In another aspect, the present disclosure can include a system for treating pain associated with arthritis. The system can include a wearable device and a control and power module in communication with the wearable device. The wearable device can include at least one optical emitter configured to deliver a light therapy, e.g., PBM,to one or more target nerves through the skin. The wearable device can also include at least one electrode configured to provide a stimulation to the one or more target nerves through the skin.Brief Description of the Drawings

[0010] The foregoing and other features of the present disclosure will become apparent to those skilled in the art to which the present disclosure relates upon reading the following description with reference to the accompanying drawings, in which:

[0011] FIG. 1 is a block diagram showing a system that can locate a delivery target on skin and deliver photobiomodulation (PBM) and / or an electrical signal transcutaneously to one or more target nerves under the skin;

[0012] FIG. 2 is a block diagram showing an alternative configuration of the system of FIG. 1 in communication with a controller;

[0013] FIG. 3 is a block diagram showing another alternative configuration of the system of FIG. 1 configured to apply PBM and / or an electrical signal to a patient;

[0014] FIG. 4 is a block diagram of at least a portion of the system of FIG. 1 applying PBM to a patient;

[0015] FIG. 5 is a block diagram of an example target locating system of the system of FIG. 1 ;

[0016] FIG. 6 includes illustrations showing aspects of an example PBM and / or electrical stimulation handheld applicator;

[0017] FIG. 7 is an illustration of another example PBM and / or electrical stimulation handheld applicator;

[0018] FIG. 8 is an illustration of another example PBM and / or electrical stimulation handheld applicator;

[0019] FIG. 9 shows additional example configurations of the skin facing side of a PBM and / or electrical stimulation applicator of FIG. 8;

[0020] FIG. 10 is an illustration of an example PBM and / or electrical stimulation handheld applicator with a moveable shield;

[0021] FIG. 11 is an illustration of a wearable patch for transcutaneously delivering PBM and / or electrical stimulation;

[0022] FIG. 12 is an illustration of another example of a wearable patch for transcutaneously delivering PBM and / or electrical stimulation;

[0023] FIG. 13 is an illustration of a plurality of tear-off wearable patches in a strip;

[0024] FIG. 14 is a block diagram showing a system for use with at least one wearable for delivery of PBM and / or electrical stimulation;

[0025] FIGS. 15 and 16 shows illustrations of example wearable devices and systems for transcutaneous delivery of PBM and / or electrical stimulation to treat pain associated with arthritis;

[0026] FIG. 17 shows an illustration of another example wearable device and system for transcutaneous delivery of PBM and / or electrical stimulation to treat pain associated with arthritis;

[0027] FIG. 18 is a process flow diagram of a method for transcutaneous application of PBM;

[0028] FIG. 19 is a process flow diagram of a method for positioning a PBM delivery device with a shield to transcutaneously apply PBM;

[0029] FIG. 20 is a process flow diagram of a method for controlling a PBM delivery device for optimal dosage delivery and / or safety; and

[0030] FIG. 21 shows illustrations of a device in use on the wrist of a patient.Detailed DescriptionI. Definitions

[0031] Unless otherwise defined, all technical terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the present disclosure pertains.

[0032] As used herein, the singular forms “a,” “an,” and “the” can also include the plural forms, unless the context clearly indicates otherwise.

[0033] As used herein, the terms “comprises” and / or “comprising,” can specify the presence of stated features, steps, operations, elements, and / or components, but do not preclude the presence or addition of one or more other features, steps, operations, elements, components, and / or groups.

[0034] As used herein, the term “and / or” can include any and all combinations of one or more of the associated listed items.

[0035] As used herein, the terms “first,” “second,” etc. should not limit the elements being described by these terms. These terms are only used to distinguish one element from another. Thus, a “first” element discussed below could also be termed a “second” element without departing from the teachings of the present disclosure. The sequence of operations (or acts / steps) is not limited to the order presented in the claims or figures unless specifically indicated otherwise.

[0036] It will be understood that when an element is referred to as being "on," "attached" to, "connected" to, "coupled" with, "contacting," etc., another element, it can be directly on, attached to, connected to, coupled with or contacting the other element or intervening elements may also be present. In contrast, when an element is referred to as being, for example, "directly on," "directly attached" to, "directly connected" to, "directly coupled" with or "directly contacting" another element, there are no intervening elements present. It will also be appreciated by those of skill in the art that references to a structure or feature that is disposed “adjacent” another feature may have portions that overlap or underlie the adjacent feature.

[0037] As used herein, the term “photobiomodulation”, abbreviated as “PBM”, can refer to the delivery of light signal(s) at one or more prescribed wavelengths and dosing schemes to one or more target nerves to achieve a desired physiological response (e.g., to reduce and / or treat acute and / or chronic pain). PBM utilizes non-ionizing light sources, including lasers, light emitting diodes, and / or broadband light sources and can be delivered by one or more emitters. In some examples, the light can have a wavelength between 250 nm and 1600 nm. However, as an example, the wavelength can be in the visible range (e.g., from 400 nm to 700 nm) and / or near-infrared range (e.g., from 700 nm to 1 100 nm) of the electromagnetic spectrum.

[0038] As used herein, the term “electrical stimulation” can refer to the application of one or more electrical signals (e.g., current(s)) with one or more predefined parameters, and optionally dosing schemes, via one or more electrodes to a patient to locate and / or estimate the depth of one or more target nerves and / or to achieve adesired physiological response (e.g., to assist PBM with reducing and / or treating acute and / or chronic pain).

[0039] As used herein, the term “dosing scheme” can refer to a schedule of one or more doses of PBM (e.g., quantities of light of one or more wavelengths) and / or doses of electrical stimulation (e.g., current at one or more parameters) to be delivered to a target area of a patient per a unit of time to treat the patient. A dosing scheme can include whether doses of the PBM and / or the electrical stimulation are applied simultaneously and / or sequentially, or a mixture thereof, a time between doses of PBM and / or electrical stimulation, one or more times of day when the dose of PBM and / or electrical stimulation is to be given, a quantity of PBM and / or electrical stimulation to be delivered, a target intensity of the light signal(s) and / or current to reach the target area, a luminance of a light source of the PBM, a power associated with the delivery of the PBM and / or electrical stimulation, an amount of PBM and / or current in the dose to reach the target area, or the like.

[0040] As used herein, the term “subcutaneous” can refer to something being situated or applied beneath (under) a patient’s skin. For instance, something located subcutaneously is located within the patient’s body under the skin. For example, the one or more target nerves described herein are subcutaneous.

[0041] As used herein, the term “transcutaneous” can refer to something being delivered through / across a patient’s skin without physically disrupting the skin barrier (e.g., light and / or electrical signals can be delivered from an external opto-electrical applicator transcutaneously to one or more subcutaneous target nerves).

[0042] As used herein, the term “patient” can refer to any warm-blooded organism. Generally, the term patient as used herein describes a human patient, but the systems, methods, and techniques described herein can also be used with respect to other warm-blood organisms (with any necessary small modifications).

[0043] As used herein, the term “physiological condition” can refer to a disorder, disease, or patient state with a neurological component and / or symptom that is at least partially treated, ameliorated, or has its progression slowed by the application of PBM and / or electrical stimulation to one or more target nerves. Physiological conditions can include, but are not limited to, injuries, surgical wounds, arthritis, hypertension, stroke,neurodegeneration of the brainstem, cardiac disease associated with elevated rostral ventrolateral medulla, headaches, facial neuralgias, or the like.

[0044] As used herein, the term “pain” refers to an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage. There generally two types of peripheral pain, nociceptive and neuropathic. Nociceptive pain is a type of pain caused by damage to body tissue and can be acute or chronic. Acute pain is relatively short in duration and subsides when the cause (e.g., injury, illness, etc.) has healed. Chronic pain may be intermittent or continuous and (1 ) persists beyond a normal recovery period of a cause (e.g., injury, illness, etc.) or (2) occurs with a chronic health condition. Acute pain can become chronic neuropathic pain in a process known as chronification.

[0045] As used herein, the term “fiber” refers to an axon, which is a long slender projection of a nerve cell or neuron in vertebrate organisms having a diameter that corresponds to conduction velocity and in some cases included a myelin sheath. Generally, a fiber conducts electrical impulses transmitting information in one or more directions throughout the body and is classified depending on the type of fiber (e.g., sensory, motor, etc.), the diameter of the fiber and / or if myelin coating is present.

[0046] As used herein, the term “nerve” refers to a bundle of fibers of different nerve cells. For example, a nerve can be a sensory nerve that includes sensory fibers, a motor nerve that includes motor fibers, a sensorimotor nerve that includes sensory and motor fibers, etc.

[0047] As used herein, the term “sensory fiber(s)” refers to part of the peripheral nervous system (PNS) (including cranial nerves) that conduct electrical impulses between a part of the body experiencing sensation and the brain / spinal cord. Sensory fibers have a range of fiber sizes. For example, sensory fibers can be classified as Acx (diameter 13-20 pm, conduction velocity 80-120 m / s, myelinated, associated with muscle spindle fibers and Golgi tendon organ); A|3 (diameter 6-12 pm, conduction velocity 33-75 m / s, myelinated, associated with all cutaneous mechanoreceptors); A8 (diameter 1 -5 pm conduction velocity 3-30 m / s, thinly myelinated, associated with free nerve endings of touch and pressure, nociceptors of the neospinothalamic tract, cold thermoreceptors); and C (diameter 0.2-1 .5 pm, conduction velocity 0.5-2.0 m / s,unmyelinated, associated with nociceptors of the paleospinothalamic tract and warmth receptors).II. Overview

[0048] Pain is the uncomfortable feeling that can signal, and accompanies, injury, illness, or the like. While most pain is acute and only lasts for the length of a normal recovery period, other pain may become chronic and extend past the normal recovery period and / or occur with a chronic health condition. In certain instances, acute pain can become chronic via chronification. Photobiomodulation (PBM) has shown the ability to treat pain, including chronic pain. In fact, PBM has been able to target small fibers within a nerve that transmit nociceptive signals conveying pain information to the brain to treat acute and / or chronic pain. Blocking these small fibers from transmitting pain information for an extended period of time can also prevent or decrease the severity of pain chronification. However, the effectiveness of PBM has been demonstrated with invasive delivery (removing skin, bone, and / or other inhibiting features before administering the PBM). For instance, application of PBM within millimeters of a target nerve is known to have a strong effect. Patients and physicians alike would prefer to achieve pain relief non-invasively compared to invasively. However, multiple, unique challenges exist when delivering PBM transcutaneously in a manner that is both safe and efficacious for a given patient (including, but not limited to, determining a location on the skin to deliver the PBM relative to the one or more target nerves for a therapeutic effect and determining the distance between the PBM delivery device and the one or more target nerves and then configuring a dose that can have an effect on the one or more target nerves while not damaging patient tissues). PBM dosing schemes also need to be customized based on patient skin tone as different skin tones affect light transmission differently. Particular safety challenges for application of PBM includes shielding the user and / or the patient from excess light of the PBM and managing repeated doses if PBM is applied at home and ensuring that heat generated by the system is kept within safe limits. Traditionally, no device has been capable of meeting these challenges and providing optimized transcutaneous PBM therapy to selectively block small fibers in patients, especially humans.

[0049] The devices used in the systems and methods described herein can solve these challenges, noninvasively and transcutaneously providing efficacious light to one or more nerves and to stop light from escaping the delivery location. Electrical stimulation may additionally and / or alternatively be applied through the same devices and systems. The devices can come in a multitude of form factors, including, but not limited to, a handheld applicator, a wearable patch, and / or a wearable device (e.g., wristband, a watch, a ring, or the like). Each form factor can include one or more shield components to stop light from the PBM from escaping a target location on the skin, which provides safety to the patient and anyone applying the PBM (e.g., safety to the eyes and other portions of the skin from light related damage). Further, each of the devices and systems are optimized to determine stimulation location(s) and dosages customized for the patient.III. Systems

[0050] Photobiomodulation (PBM) has shown the ability to treat and / or block nociceptive pain, both acute and chronic. As shown and described herein, PBM can be applied noninvasively and transcutaneously to target one or more specific nerves, each including at least one sensory fiber, under a patient’s skin to achieve the strong pain relief previously only associated with invasive approaches. The sensory fiber can conduct, for instance, signals related to pain, inflammation, arthritis, symptoms of arthritis, and / or heat hypersensitivity. In some instances, an electrical signal can be applied transcutaneously, additionally or alternatively. As described herein, the PBM and / or electrical signal can be applied transcutaneously via a handheld applicator, one or more wearable patches, a wearable device, any combination thereof, or the like. The transcutaneous PBM can be configured based on information from devices / components that can determine a location for applying PBM on a patient’s skin, depth of the one or more target nerves under the patient’s skin, and / or proper dosage for the specific patient. Application of the transcutaneous PBM can employ one or more safety measures, including safety checks, a shield, or the like, to protect the eyes of the patient or a caretaker from potential light damage and / or manage temperatures associated with the PBM.

[0051] FIG. 1 shows an example system 100 that can deliver PBM transcutaneously to one or more target nerves (shown as one nerve for ease of illustration and description) under the skin. The system 100 can include an external PBM delivery system 10 that can be used to deliver PBM transcutaneously through a location on the patient’s skin to one or more target nerves. The PBM delivery system 10 can include at least (1 ) one or more optical emitters (optical emitter(s) 12) and (2) a shield 14. In some instances, the system 100 can also include a target locating system 20 to determine a location where the PBM delivery system 10 should apply the PBM through the patient’s skin. The target locating system 20 can include at least (1 ) a recording device 22 and (2) a querying device 24, which can provide information used when determining the location of the target nerve and / or where the PBM delivery system 10 should apply the PBM through the patient’s skin.

[0052] As noted, the PBM delivery system 10 can include one or more optical emitter(s) 12 and a shield 14. The optical emitter(s) 12 can include a light source. The light source can, for instance be coupled to a fiber optic cable. The light source can include, LEDs, lasers, or the like connected to a light generator and / or power source (not shown in FIG. 1 ). The light source can be configured to emit light of at least one wavelength. For example, the wavelength can be from 400 nm to 1200 nm, more preferably from 600 nm to 1000nm, and most preferably from 800 nm to 850 nm. The optical emitter(s) 12 can emit light that is continuous and / or pulsed. The optical emitter(s) 12 can receive dosing parameters to be able to configure the dose of PBM. For example, the parameters can include an application time (e.g., 1 second, 10 seconds, 30 seconds, 2 minutes, 3 minutes, 10 minutes, 1 hour, 2 hours, 3 hours, 4 hours, or the like), an energy (e.g., 100 mW, 300 mW, 1 W, 2 W, 4W, 10 W, 20 W, 50 W, 100 W or the like, depending on the spot size of the optical emitter 12 and known safety limits), or the like. For instance, in cases of pulsatile light delivery the power can be higher if the application time is longer, and the duty cycle is low. The PBM delivery system 10 can deliver multiple doses of PBM at different times, e.g., another dose of PBM, having the same or different parameters, can be applied at a later time. In some instances, the power source (not illustrated) can include one or more batteries and / or a connection configured to receive line power.

[0053] The optical emitter(s) 12 can orient along the one or more nerves such that the block provided by the application of the PBM is stronger (e.g., more of the one or more nerves are blocked). For instance, the optical emitter(s) 12 can extend / be positioned in an orientation perpendicular to the one or more nerves to increase a likelihood of having light directed at the one or more nerves. In another instance, the optical emitter(s) 12 can extend / be positioned in an orientation perpendicular to the one or more nerves to deliver light to multiple nerves simultaneously.

[0054] The shield 14 can extend outward around at least a portion of the optical emitter(s) 12 (illustrations provided, for example, in FIG. 10) and can block escape of at least a wavelength of the dose of PBM. The shield 14 can have any configuration and position that can block the escape of extra or errant light from the PBM application. Example shield configurations are shown and described in more detail in FIGS. 6-10. The shield 14 can be made of a material, such as glass and / or one or more polymers, that can be processed to maintain transparency but include one or more dyes that can be at least partially opaque to specific wavelengths and / or intensities that can stop at least some of the wavelengths of the dose(es) of PBM applied by the PBM delivery system 10. In one instance, the shield can filter out the wavelengths of the high intensity light used for the transcutaneous PBM and leave others. In some instances, the shield 14 may be transparent to light outside the wavelengths of the dose(s) of PBM, e.g., allow through visible light so the user can see through the shield. The shield 14 can protect eyes of the patient and / or a caregiver administering the PBM from the PBM wavelengths.

[0055] In some instances, as noted, the system 100 can also include a target locating system 20 for determining the location on the skin for using the PBM delivery system 10. The PBM delivery system 10 and the target locating system 20 can be embodied as separate components that can switch positions over the determined delivery location (as shown). Alternatively, the PBM delivery system 10 and the target locating system 20 can be embodied in a single housing (not shown in FIG. 1 ) where each can be positioned such that the PBM delivery system 10 can deliver light at the delivery location determined by the target locating system (e.g., co-located, positioned around a central point, etc.). The PBM delivery system 10 and the target locatingsystem 20 can be, in some instance, removably coupled together. It should be noted that in FIGS. 2 and 3 the PBM delivery system 10 and the target locating system 20 are shown side by side for illustration purposes only and it should be understood they can be in any position relative to one another, including over the same location on the skin.

[0056] The target locating system 20 can include at least a recording device 22 and a querying device 24. In some instance the recording device 22 and the querying device 24 can be embodied in a single combination device having the functionality of both. However, in other instances, the recording device 22 and the querying device 24 can be in separate devices, but able to communicate with one another. The querying device 24 can test various locations on the skin of the patient for at least one identifying parameter (e.g., one or more visual parameters, one or more electrical parameters, one or more thermal parameters, or the like) indicative of the presence or absence of one or more target nerve. The querying device 24 can be, for instance, at least part of an electrical stimulation system and / or an imaging device such as an optical coherence tomography (OCT) system, a magnetic resonance (MR) neurography system, a positron emission tomography (PET) or other radiotracer imaging system. It should be understood that if an electrical stimulation based querying device is used, a recording device is not required to be used, especially if the electrodes and the light emitter are arranged such that the location can be identified by stimulation and then with the device in that position (the light can be turned on to target the nerve that had been electrically stimulated).

[0057] The recording device 22 can be, for instance, any device comprising at least a processor and a non-transitory memory to receive and / or analyze information from the querying device 24. The recording device 22 can use the information from the querying device 24 to determine a location of the one or more target nerves under the skin of the patient, each including at least one sensory fiber (e.g. that can conduct signals related to pain, inflammation, arthritis, symptoms of arthritis, and / or heat hypersensitivity). The location can be marked such that PBM delivery system 10 can find the marked location and the optical emitter 12 can deliver a dose of PBM through a patient’s skin to the one or more target nerves. The location can be marked by an identifying mark on and / or under the patient’s skin. The identifying mark can be, for instance, a tattoo, an implanted or external radio frequency identification device, a series of implantedquantum dot codes, or the like. For example, the tattoo may be a dot the color of a freckle or may use a dye that is not visible to the human eye in daylight (or at all) but is detectable by the PBM delivery system 10 or is visible under LIV light. In the latter case, in some instances, the PBM delivery system 10 can deliver a low amount of UV light to visualize the tattoo, allowing correct positioning of the system for PBM delivery 10. Alternatively and or additionally, record of the location can be determined based on a reported paresthesia response from the patient (e.g. to detect a threshold and / or sensory topography). It should be appreciated that the recording device 22 is not necessary in every configuration and instead is optional and only present in certain cases).

[0058] Referring now to FIG. 2 the system 1 10 can include all of the components of FIG. 1 , but also includes a controller 30. While the controller 30 is shown as separate from and in electrical communication (wired and / or wireless) with the PBM delivery system 10 and the target locating system 20, it should be understood that the controller can be in a combination device and / or the same housing as the PBM delivery system 10 and / or the target locating system 20. Furthermore, it should be understood that the controller 30 may in some instances include some or all of the functionality of the recording device 22 and / or the querying device 24 of the target locating system 20. For instance, the controller 30 and the recording device 22 can be the same device and / or share functionality such that the target locating system 20 can record at least one identifying parameter related to the one or more target nerves under the skin of a patient. It should also be understood that the controller 30 can, additionally or alternatively, determine one or more of the parameters for the application of light by the PBM delivery system.

[0059] The controller 30 can include a non-transitory memory 32 that can store instructions and / or recorded data and a processor 34 that can execute the instructions. In some instances, the controller can include an electrical and / or a light generator 36. The controller 30 can operate in real time for the detection of the location and / or depth of the one or more target nerves and to configure the dose parameters of the PBM delivery. The controller 30 can identify a location of the one or more target nerves based on the at least one identifying parameter determined by the querying device 24. Thecontroller 30 can then estimate a depth of the one or more target nerves under the skin based on the at least one identifying parameter and configure dose parameters for a dose of PBM to be applied to modify conduction in the at least one sensory fiber related to pain in the one or more target nerves based on the location and the depth of the one or more target nerves. The dose parameters can include at least one or more of a power, a wavelength, a frequency, and a duration. The controller 30 can also execute instructions to calibrate the dose of PBM such that the at least one identifying parameter includes and / or is based on the patient’s skin tone. Skin tone can change the absorbance of certain wavelengths of light, and the controller 30 can correct the parameters and / or add a parameter to account for the patient’s skin tone.

[0060] Also shown in FIG. 2, the PBM delivery system 10 can in some instances include one or more electrodes (electrode(s)) 16 that can provide electrical stimulation in concert with delivery of PBM for therapeutic purposes. The electrical stimulation can be provided concurrently and / or separately from the PBM delivery. For instance, in some pain indications stimulating the more excitable large fibers with electrical stimulation and blocking small fiber activity with PBM can provide complementary therapy. In another instance, the electrode(s) 16 may share functionality with the target locating system 20 (although shown in the PBM delivery system 10) and can apply electrical stimulation to locate the one or more target nerves and / or estimate the depth under the skin of the one or more target nerves, as described in greater detail later. In still other instances, the electrodes can be coupled to the shield 14 (or any structural component serving that function) and used by the controller 30 to determine if the shield 14 is in a proper shielding position before PBM is delivered.

[0061] FIG. 3 shows an example of system 120 where the PBM delivery system 10 and the target locating system 20 are both within a single housing. The controller 30 can be within the housing or can be external to the housing and in wireless and / or wired communication with the rest of system 120. In the example of FIG. 3 the optical emitter(s) 12 and / or electrode(s) 16 and the querying device 24 are shown side by side for ease of illustration, but it should be understood that they may be in any configuration relative to the skin of the user. The querying device 24 can test locations on the skin of the patient to find the location on the skin over the one or more target nerves (e.g., viaoptical detection, electrical detection, or the like). The controller 30 and / or the recording device 22 can determine when the location on the skin is found and the skin can be marked with an identifying mark (manually and / or by the querying device and / or a marking device (not shown)). Once the location on the skin is determined the querying device 24 and the recording device 22 and / or the controller 30 can estimate the depth of the one or more target nerves under the skin (e.g., via optical detection, electrical detection, or the like). The controller 30 can use the estimated depth of the one or more target nerves under the skin as at least one input to determine the dose of PBM to be applied. Other inputs can include, but are not limited to, skin tone, the condition to be treated, an overall dosage scheme prescribed the patient, the number of the one or more target nerves to be treated, thermal conditions of the skin and other tissues between the one or more nerves and the optical emitter(s) 12, or the like. The optical emitter(s) 12 can apply the PBM to the one or more target nerves through the patient’s skin and silence and / or reduce conduction in the at least one small diameter fiber in the one or more target nerves. The shield 14 can cover over at least the optical emitter(s) 12 to prevent the escape of errant light from the PBM application. The shield 14 can be a portion of the system 120 (e.g., a layer in the housing, a skin facing surface of the housing, an extruded shape from a main housing body, or the like) or can make up the entire housing material of the system (e.g., an applicator body can be entirely made of a shielding material).

[0062] FIG. 4 displays an example system 130 that shows the use of the controller 30 and the PBM delivery system 10 after the target locating system 20 has determined the location on the skin over the one or more target nerves and / or estimated the depth of the one or more target nerves under the skin. In FIG. 4, the skin is marked with an identifying mark (shown for ease of illustration as a black circle) indicative of the target area on the skin for the PBM to be applied. The identifying mark can be marked on and / or under the patient’s skin. The identifying mark can be, but is not limited to, a tattoo, an implanted or external radio frequency identification device, and / or a series of implanted quantum dot codes. The PBM delivery system 10 can include a camera 18 can determine a location of the identifying mark. The camera 18 can detect the identifying mark and send information related to the identifying mark to the controller 30(e.g., the processor) and the controller 30 can process the information related to the identifying mark to determine if the PBM delivery system 10 is positioned correctly over the target area / location to provide the PBM. In one instance, the controller 30 can prevent the PBM delivery system 10 from applying the PBM if the identifying mark is not detected by the camera 18. Alternatively and / or additionally, the camera 18 can be used to detect the skin tone of the target location on the skin (e.g., general skin tone, skin tone with the marker added, any skin discolorations and / or changes such as freckles or birthmarks, etc.), the camera can send the detected skin tone to the controller 30 and the controller 30 can, if needed, change and / or add one or more parameters the dose of the PBM based on the skin tone at the target location on the skin. The controller 30 can send the one or more parameters of the dose of the PBM (also referred to as dose parameters) to the optical emitter(s) 12 to apply the dose of the PBM. The dose parameters can include wavelength, power, frequency, duration, pulsatilty, etc. The controller 30 can also implement one or more dose management elements. The one or more dose management elements can include PBM boluses configured by a clinician and deliverable by the optical emitter(s) 12 when the controller 30 instructs the PBM delivery system 10 to deliver the PBM.

[0063] The PBM delivery system 10 can in some instances include one or more sensors 19 that can detect information and / or data that can be provided as feedback to the controller 30. The one or more sensors 19 can include a temperature sensor, a photodetector, a reflector, an electrical sensor (e.g., an impedance sensor, or other sensor that can sense current), or the like. For example, the feedback sent from the one or more sensors 19 and received by the controller 30 can include information (data signal or other type of signal) about light received by the skin, temperature of the skin, etc. The feedback can allow the controller 30 to configure and / or reconfigure the PBM dose parameters (and / or electrical signal parameters if electrical stimulation used) more precisely so that the PBM (and / or the electrical signal) delivered to the target area matches the prescription. As an example, a temperature sensor can be configured to sense a temperature of the skin at and / or near the target area, and the controller 30 can determine the PBM dose parameters (and / or electrical signal parameters if electrical stimulation used) based on a pre-determined temperature management limit for thetarget area (e.g., before a threshold level of damage occurs) and / or prevent application of PBM (or electrical stimulation) if a detected temperature is above the threshold until the detected temperature decreases to a safe level.

[0064] FIG. 5 shows the target locating system 20 in greater detail (the targeting system is optional and only present in certain cases). The target locating system 20 can include the querying device 24 and the recording device 22. The target locating system 20 can optionally include a separate controller 30 (including a memory and processor, not shown) and / or the controller 30 can be at least partially embodied in the recording device 22 and / or the querying device 24. In one instance the target locating system 20 can include an imaging wand 26 that can be moved over a target area on a patient’s skin to record an image comprising the one or more target nerves. The imaging wand 26 can be used for at least one of optical coherence tomography, magnetic resonance neurography, positron emission tomography, radiotracer imaging, or ultrasound.

[0065] In another instance the target locating system 20 can include an electrical stimulation device 28 that includes one or more electrodes (electrode(s)) 38 that can electrically stimulate the one or more target nerves through the skin. The electrical stimulation device 28 can also include at least one electrode that can sense a stimulation level of the one or more target nerves. It should be noted that if the target locating system 20 and the PBM delivery system 10 are embodied in a single device the electrodes 38 (of the target locating system) and the electrodes 16 (of the PBM delivery system) may be the same electrodes. The controller 30 (and / or the recording device 22) can estimate a distance and / or depth from the skin surface to the one or more target nerves based on the sensed stimulation level. In some instances, the patient can selfrespond (e.g., verbally to a clinician, or through a user interface (not shown) of the controller 30 or an external device (not shown) in communication with the controller) to indicate when a full level of block is felt (e.g., paresthesia, no pain, etc.). As an example, the patient can report a feeling of tingling or paresthesia at a given location on the body, when the given location matches with a known location associated with stimulation of the target nerve the location of the target nerve is found and PBM can be delivered via the PBM delivery system 10. In some instances, the controller 30 can then estimate thedepth of the one or more target nerves under the skin based on the parameters of the electrical stimulation being applied at that time before delivery of the PBM.

[0066] FIG. 6 shows illustrations of alternative systems 200 and 250 that can combine at least the PBM delivery system and the target locating system in a single handheld applicator. FIG. 6, element A, shows a system 200 that can combine PBM delivery with imaging and FIG. 6, element B, shows a system 250 that can combine PBM delivery with electrical stimulation. The controller may be at least partially within the applicator body 202 and / or external to and in wired and / or wireless connection the applicator body (e.g., a computer, tablet, smartphone, etc. not shown). The applicator body 202 can include the shield (e.g., shield 14) and can hold any basic circuitry and / or electrical components not specifically shown, including but not limited to a memory, processor, battery and / or connection to an external power source, wireless transmitter / transceiver, or the like). Each example instance can be coupled to a shield as described.

[0067] FIG. 6, element A shows an illustration of a system 200 that can combine imaging and PBM delivery in a single handheld applicator. The applicator body 202 can, in addition to the components previously discussed, include an imaging component 208 and one or more optical emitters (optical emitter(s)) 204 with at least sensing and / or delivery portions on / extending from a skin facing side of the applicator. The system 200 can be used to perform imaging of one or more target nerves to identify the location and / or depth of the one or more target nerves (by the imaging component 208) and to then deliver a dose of PBM (by the optical emitter(s) 204). The dose of PBM can be delivered for diagnostic purposes, such as to determine if another more invasive type of nerve block would be appropriate for a patient, to determine conduction information of the one or more target nerves, or the like. The dose of PBM can be delivered for therapeutic purposes, such as treating and / or at least partially preventing pain such as nociceptive pain by blocking and / or at least partially blocking small fiber(s) that conduct a pain signal in the one or more target nerves. The applicator body 202 can be, for instance a transducer or wand for a larger imaging system with an integrated PBM delivery system (including the shield 210). The imaging component 208 can be, for instance at least part of an optical coherence tomography (OCT) system, an ultrasoundsystem, a magnetic resonance (MR) neurography system, a positron emission tomography (PET) system or other radiotracer detection system, or the like. One preferred imaging system may be high resolution ultrasound, which can provide suitable resolution and depth information for nerves under the skin.

[0068] In one instance, the optical emitter(s) 204 can deliver the PBM dose concurrently with the imaging component 208 imaging the patient to provide feedback of the location of and / or distance to the one or more target nerves in real time - so the controller (not shown) can improve the dose estimate in response to the feedback at a given time. The applicator body 202 can serve as / include a shield 210 that can shield the light of the PBM delivered by the optical emitter(s) and protect the eyes of the patient, a clinician, a caregiver, or anyone else in the vicinity. The system 200 may be configured to prevent PBM delivery if the applicator body 202 is not in contact with the body (e.g., using a force sensor, impedance sensor, or the like (not shown)) providing feedback to the controller. For example, if the wand is separated from the skin of the patient the optical emitter(s) 204 can be automatically turned off (e.g., by the controller or an internal analog switch). The controller can further include one or more models and / or lookup tables to estimate dose delivery and can provide graphical information (e.g., through a display of the controller and / or in communication with the controller) to the clinician or other user about light that can be delivered / is being delivered to the tissue. Examples of such information can include the trajectory of the light emission axis of the optical emitter(s) 204, dose information (e.g., as contours), a selected target, recommended wavelength, time, power, or the like, and / or expected outputs such as days to reduced transmission, description of reduced transmission as a function of time, or the like. In some instances, a clinician can use the system 200 with the controller to keep records and / or automate dose estimation and recommendations. The one or more models can account for skin tone information, which can be provided by the imaging component 208.

[0069] In other instances, not shown, the PBM delivery system can be removably connected to (e.g., mechanically, magnetically, etc.) a wand and / or transducer of an imaging system. For example, a fiber optic jacket or other bracket can be used to hold a fiber optic cable (e.g., an example optical emitter 204) on a portion of an imagingwand / transducer instead of using a fully integrated device (it should be noted that this approach allows for the imaging component to be changed as necessary per patient case). Such a configuration may be used with photoacoustic imaging for diagnostic purposes, for example. One difference between a diagnostic setup and a therapeutic setup is that a therapeutic setup can provide wavelengths and doses appropriate for therapeutic effect. The diagnostic setup may not utilize complex models and instead include basic open or closed loop control of levels of PBM.

[0070] FIG. 6, element B, shows an illustration of a system 250 that can combine electrical stimulation and PBM delivery in a single handheld applicator. The applicator body 202 can, in addition to the components previously discussed, include one or more electrodes (electrode(s)) 206 and one or more optical emitters (optical emitter(s)) 204 with at least sensing and / or delivery portions on / extending from a skin facing side of the applicator. It should be noted that while the electrode(s) 206 and optical emitter(s) 204 are shown protruding from the main body of the application this is only one example configuration and any others, including those shown in other figures are contemplated. Similar to system 200, the system 250 can be used to perform electrical stimulation of one or more target nerves to identify the location and / or depth of the one or more target nerves (by the electrode(s) 206) and to then deliver a dose of PBM (by the optical emitter(s) 204). The dose of PBM can be delivered for diagnostic purposes, such as to determine if another more invasive type of nerve block would be appropriate for a patient, to determine conduction information of the one or more target nerves, or the like. The dose of PBM can be delivered for therapeutic purposes, such as treating and / or at least partially preventing pain such as nociceptive pain by blocking and / or at least partially blocking small fiber(s) that conduct a pain signal in the one or more target nerves. It should be noted that the system 250 can provide PBM delivery to the skin at the exact placement of one or more of the electrodes 206 without moving the system with the annular design shown. In one instance, the electrical stimulation can be provided concurrently with delivery of the PBM dose (e.g., for therapeutic purposes).

[0071] At least a portion of the applicator body 202 (the base body or the protruding portion(s)) can include the shield 210 and can protect the eyes of the patient, the clinician, and / or any others in the vicinity from the light of the PBM delivery. Theshield 210 can be any material that can prevent the escape of the light of the PBM. In one instance the shield can prevent the escape of PBM wavelengths of light only. The shield can be, for instance, on the skin facing and / or touching side of the applicator body 202 or on all or a portion of the applicator body. The system 250 can be configured to prevent PBM delivery if at least a portion of the applicator body 202 is not in contact with the skin. For example, if at least the portion of the applicator body 202 including the optical emitter 204 is separated from the skin of the patient the optical emitter can be automatically turned off (e.g., by the controller or an internal analog switch). The system 250 can detect whether the system is in sufficient contact with the skin of the patient based on, for instance, impedance and / or other electrical characteristics. The controller can stop or refuse to instruct the PBM delivery system to deliver the PBM dose when the system is not in contact with the skin of the patient.

[0072] As shown in FIG. 6, element B, the system 250 can include an annular cathode electrode and / or an annular anode electrode (+ and - electrode(s) 206) for electrical stimulation that can each or alternatively include a lumen for an optical emitter 204 to deliver PBM. It should be noted that the electrode(s) 206 can be annular, substantially annular, partial arcs, or the like around an optical emitter 204 or a lumen for the optical emitter. The lumen can have an opening extending in the approximate center of the substantially annular, annular, or ring shaped at least one electrode 206 and can be connected to the optical emitter 204 to provide the PBM dose to the one or more target nerves through the skin. The electrode(s) 206 can be for example, gold electrodes. The electrode(s) 206 can be insulated at least immediately adjacent the area where the electrode(s) 206 touch the skin to improve specificity of stimulation and / or to be able to use the electrode’s contact with the skin as a more reliable detector of proper contact with the body to ensure shielding (e.g., shield 210) is in place by using the electrode as an impedance detector, and if impedance goes high (e.g., not touching skin) then the light cannot be delivered. The electrode(s) 206 can also be used as part of the target locating system to estimate the distance from the skin surface to the one or more target nerves. The controller (not shown) can use the stimulation threshold of the electrical stimulation to estimate the distance and then estimate the dose of PBM and / or one or more dose parameters to achieve the desired therapeutic effect based on theestimated distance and / or the stimulation threshold directly. In some instances electrical stimulation of the one or more target nerves can be confirmed by at least one of patient self-reporting paresthesia and the extent of the paresthesia’s distribution, recordings by a recording electrode (e.g., as commonly used for a nerve conduction test), a visible motor responses (if the one or more target nerves comprise mixed fibers), and / or a recorded motor response using electromyography (EMG) (if the one or more target nerves comprise mixed fibers).

[0073] The optical emitter(s) 204 can deliver the PBM dose concurrently with the electrode(s) 206 delivering electrical stimulation to the patient to provide feedback of the location of and / or distance to the one or more target nerves in real time - so the controller (not shown) can improve the dose estimate in response to the feedback at a given time. The controller can further include one or more models to estimate dose delivery and can provide graphical information (e.g., through a display of the controller and / or in communication with the controller) to the clinician or other user about light that can be delivered / is being delivered to the tissue. Examples of such information can include the trajectory of the light emission axis of the optical emitter(s) 204, dose information (e.g., as contours), a selected target, recommended wavelength, time, power, or the like, and / or expected outputs such as days to reduced transmission, description of reduced transmission as a function of time or the like. In some instances, a clinician can use the system 200 with the controller to keep records and / or automate dose estimation and recommendations. The one or more models can account for skin tone information (e.g., based on a look up table of how skin tone effects different parameters of PBM), which can be provided by a separate imaging component (not shown) and / or stored in memory.

[0074] As shown in the alternative example of FIG. 6, element C, more than one electrode 206 can be positioned around the edge a lumen for an optical emitter 204.Two electrodes 206 are depicted as partial annulus but it should be understood that any number one or greater can be used. For instance, the larger the circumference of the optical emitter 204, the more electrodes can be positioned to increase the likelihood that the impedance measurements are accurate and the PBM delivery portion of system 250 is not partially lifted from the skin. The two electrodes 206 can provide stimulationand recording functions for the controller (not shown) to confirm that at least a portion of system 250 is in contact with the skin, as determined by tissue impedance measurement(s). Note that these electrodes 206 may or may not be the same as those used for the electrical stimulation. As previously stated, the controller can stop the delivery of PBM and / or not allow the start of PBM delivery when the impedance is above a threshold indicating a possible open circuit (e.g., the system 250 is no longer being held to the skin sufficiently). In this example, the close proximity of the two electrodes 206 can makes it difficult for a user to create a scenario where the PBM delivery is ON and unshielded, further providing protection from the eye safety hazard.

[0075] Referring now to FIG. 7, is another example system 300 include a handheld PBM and electrical stimulation applicator 301 connected (wired and / or wirelessly) to a controller 308. It should be noted that the PBM and electrical stimulation applicator may also be coupled to a shield as described above. The handheld PBM and electrical stimulation applicator 301 can include a plurality of electrodes 306 (seven shown, but any number can be included) around a circumference of at least one optical emitter (optical emitter(s)) 304. As an example, the skin facing side of the applicator body 302 can be the shield 310, but it should be understood any portion of the applicator body can include the shield. If even one of the electrodes 306 is determined by the controller 308 to not be against the skin, then the controller can automatically turn off light delivered by the optical emitter(s) 304. The electrode(s) 306 can also and / or alternatively be used for electrical stimulation of the one or more target nerves. The electrical stimulation (with the controller 308) can be used to determine the location of the one or more target nerves, estimate depth of the one or more target nerves, and / or for therapeutic purposes. For instance, pairs of electrodes 306 on opposite sides of the circumference of the optical emitter(s) 304 and / or an opening for the optical emitter(s) can be used as anode-cathode pairs for the electrical stimulation. The stimulation threshold used to excite the one or more target nerves can be captured by the controller 308 and used to set the amount of light (or other parameters) for the dose of PBM that should be delivered. It should be noted that the light emitting region (including the optical emitter(s) 304) can be any size and / or shape sufficient to deliver the prescribed dose of PBM to a target area at and below the skin within safety guidelines of energydensity and power density. For instance, the area of the light emitting region can be from less than 1 mm2to less than 10 cm2, such as 1 mm2to 3 cm2, 0.5 mm2to 5 cm2, or the like.

[0076] The controller 308 can be external to the applicator body 302 (as shown) or can be inside the applicator body 302. In some instances, the functionalities of the controller 308 can be implemented at least partially in the applicator body 302 and at least partially in an external device. The controller 308 can include at least a non- transitory memory and a processor and can have any of the functionality of the controllers described herein. When the controller 308 is external to the applicator body 302, then the controller and the applicator body can be connected with a wireless and / or wired connection. The controller 308 can includes a user interface (e.g., touch screen, keyboard, mouse, buttons, knobs, levers, switches, or the like) and / or a display for controlling the electrical stimulation and PBM light delivery settings and parameters. In some instances, the controller 308 can include a power source (not shown). An external device (e.g., smart phone, computer, tablet, or the like) (not shown) can additionally be in communication with the controller 308.

[0077] Referring now to FIG. 8, another example handheld applicator system 400 for PBM delivery and electrical stimulation is shown with a flexible shield 408 that extends out from the body of the applicator (light delivery path 404. The shield 408 can include one or more patches 410 (shown as two) that can stick (e.g., using a biologically safe adhesive, suction, pressure, or the like) to the skin surface. In some instances, the one or more patches must be adhered to the skin before the controller 402 can deliver the PBM through the light delivery path 404 (e.g., safety mechanism). The light delivery path 404 can include, for example a fiber optic cable. Each of the patches 410 can include at least one electrode 406 and the controller 402 can use impedance measurements to determine if each of the patches is adhered to the skin to contain the PBM light. In one instance, the electrode(s) 406 can be gel patch electrodes, which can be malleable and form to the skin. A plurality of patches 410 and / or electrode(s) 406 can be used to enclose a majority of the periphery of the shield 408 to entrap the light of the PBM between the body of the patient and the shield. The shield 408 can be a replaceable component of the system 400. In such cases the controller 402 can includeinstructions to not delivery PBM unless the shield 408 is adhered to the skin and connected (e.g., in electrical communication) with the light delivery path 404 (e.g., correct connection can flip a switch or the like). The shield 408 can be reflective to or absorb at least the wavelengths of the PBM.

[0078] For a use at home version of the system 400 (e.g., used without a clinician present) the shield can have a small circumference, for example, to improve the likelihood that the shield 408 entraps a majority or all of the light of the PBM. The system 400 can require the electrode(s) 406 to be in contact with the skin for the controller 402 to turn the system on. The controller 402 can be pre-programmed with a number of doses and / or amount of light that can be delivered under a prescription by a clinician. The dose delivery (PBM and / or electrical stimulation) can be limited in time. For example, the system 400 can be pre-programmed to deliver one dose every three days (or any conceivable dose per unit time, minute, hour, day, etc.), up to a maximum number of doses (e.g., 30, 60, 100, etc.), like the doses in an inhaler but monitored usage. This would prevent a patient from delivering too many doses in a short period of time (e.g., causing harm to skin, tissues, and / or the one or more nerves, reducing longterm effect(s) from going off prescription, etc.). A patient would have to bring the system 400 back to a clinician to program the system with additional dosages, providing an opportunity for evaluation of patient progress. Alternatively, the reprogramming may be done remotely over an internet connection. The prescribed therapy can be PBM delivery and / or electrical stimulation.

[0079] FIG. 9 shows example shapes of the bottom area of different examples of the shields 408a, b with different, but not exclusive, shapes. In FIG. 9, element A, the shield 408a is in a diamond shape and in FIG. 9, element B, the shield 408b is in a hexagon shape. It should be understood that the shapes shown are only for illustration and any shape, polygon or otherwise, that can be contemplated can be used with system 400. The electrode(s) 406 can be positioned at intervals around the edges of the shields 408a, b. The electrode(s) 406 can be positioned at corners of the shields 408 a, b periphery (as shown) along the edges(s), and / or as best determined to maximize the ability to evaluate contact with the body through impedance measurement. At least one electrode 406 can also be positioned near the opening of the light delivery path 404. Inone example, electrode 406 can be in a ring around an end of the optical emitter 412 and / or the opening. While not shown in FIG. 9 it should be understood that the shields 408a, b can include one or more adhesive portions for connecting to the skin. The adhesive portions can be on any area of the shields 408 a, b not blocking an electrode 406 and / or an optical emitter 412.

[0080] Referring now to FIG. 10, another example system 500 for a PBM applicator is shown. The system 500 can integrate imaging and / or electrical stimulation with the PBM delivery as well. The system 500 can include an applicator body 502 having a portion that extends in an elongated, narrow shaft (narrower than the main applicator body) from at least one side of the main applicator body. In system 500 the shield 506 is positioned on the shaft and can slide up and down the shaft (as shown in elements A and B). It should be noted that the shield 506 is shown shaped like a cone but can have any shape that would perform the functionality of the shield as previously described (e.g., shield 14, 210, 408, etc.). The shield 506 can be on a slider on the shaft of the system 500. When the shield 506 is in the up position (see element A), the user (patient or caregiver) can see where the light emitting region 508 is located on the skin, but the light cannot be turned on to deliver the PBM therapy. After positioning the light emitting region 508, the user can move the shield to the down position. When the shield 506 is in the down position (see element B) system 500 can deliver PBM therapy. In one instance the system 500 can include an indicator (e.g., a light, a display, a speaker, or the like) that can inform the user when the shield is up or down, when PBM light therapy is being applied, if PBM light therapy is done being applied, if the system is not ready, or the like. For example, system readiness can depend on the shield 506 being in place, the dose being available at the time per clinician programming, dose parameters having been defined and recorded in memory, adequate battery power, or the like. The information can be provided visibly and / or audibly. In one example, the shield 506 can be reflective and can include a photodetector (not shown) that can detect the proximity of the shield to the skin to ensure the emitter is in contact with the skin and the shield is secure. The photodetector can connect to a controller (not shown) that runs the PBM delivery.

[0081] It should be noted that any systems and devices described herein may be designed for home use, rather than just use in a clinical setting. A device or system for home use can be loaded with a prescription of doses by a clinician and sent home with the patient (e.g., with safety checks to ensure the prescribed dosing scheme cannot be changed outside of safe limits). The amount of light delivered as the PBM therapy can be managed over a given time period and at the end of each prescription period the patient can be reassessed. For example, a prescription can include a total period of time the light doses can be applied, the time per dose the light can be applied, the total quantity of light that can be applied, the quantity of light that can be applied per dose, a maximum number of doses per a time period, a maximum number of doses, an expiration date for the prescription, or the like.

[0082] FIG. 11 shows an example of a wearable patch 600 that can deliver at least PBM to one or more target nerves through the skin, transcutaneously. While not shown in FIG. 11 , the wearable patch can be in electrical communication with a controller that can control at least delivery of the PBM. As shown in FIG. 11 , element A, the wearable patch 600 can include at least a skin side layer 610 and a shielding layer 620. The shielding layer 620 can be above the skin side layer 610. Other layers (not shown) may be between the shielding layer 620 and the skin layer 610 or above the shielding layer. The wearable patch can be removable. In some instances, the wearable patch can be reusable. As shown in FIG. 1 1 , element B, the skin layer 610 can include at least an adhesive portion 612 that can attach to a patient’s skin and at least one opening 616 configured to facilitate transmission of at least a dose of PBM through the skin. The dose of PBM can have dose parameters (e.g., wavelength, power, energy, pulsatility, frequency, etc.). The dose of PBM can be sent through the skin to at least one target nerve to modify conduction in at least one sensory fiber of the at least one target nerve related to pain, inflammation, arthritis, symptoms of arthritis, and / or heat hypersensitivity. The shielding layer 620 can include at least one material (shielding material 622 shown in element C) configured to block escape of at least the wavelength of the dose of PBM. In one instance, the wearable patch 600 can be used with a separate optical emitter 614 (e.g., handheld) and positioned with the patch to deliver PBM through the opening 616. In another instance, the wearable patch 600 can includean optical emitter 614 that can be positioned relative to the opening 616 such that the dose of PBM travels out the opening towards the skin of the patient. The wearable patch 600 can include a hydrogel layer (not shown) between the opening 616 and the skin that the dose of PBM can be emitted through. Additionally, and / or alternatively the adhesive portion 612 and / or the opening 616 can be configured to facilitate delivery of an analgesic (fluid, solid, and / or gas) (e.g., lidocaine or another pharmacological agent) in concert with the PBM delivery, which can in some instances, increase the therapeutic effectiveness of the PBM delivery. The wearable patch may include a reservoir layer (not shown) above the skin side layer 610 to hold the analgesic.

[0083] The optical emitter 616 can be positioned at least partially within the skin side layer 610, the shield layer 620, and / or another layer (not shown). In another instance, the wearable patch 600 can include an optical fiber coupled to an optical emitter (e.g., external to or at least partially internal to the wearable patch) and configured to extend through the opening to deliver the dose of PBM. The skin side layer 610 can also include one or more electrodes 618 (shown as two but should be understood could be any number one or greater in any configuration and / or positioning). For example, the skin side layer 610 can include two electrodes 618 positioned on opposite sides of the opening 616. The two electrodes 618 can be configured to provide electrical stimulation to identify a location and / or depth under the skin of at least one target nerve and / or confirm a location and / or depth under the skin of the at least one target nerve (if already pre-identified). The two electrodes 618 can be configured to delivery stimulation before PBM can be delivered, concurrently with delivery of the PBM delivery and / or after delivery of the PBM. The two electrode 618 can provide electrical stimulation for therapeutic effect in addition and / or alternatively to the PBM delivery. The two electrodes 618 can also be used to determine if the wearable patch 600 is sufficiently in contact with the skin to block escape of at least part of the wavelength(s) of the PBM via tissue impedance measurements, as described previously. Another sensor (not shown) such as a pressure sensor, suction sensor, photodetector, or the like can be used to determine wearable patch 600 positioning on the skin in place of the electrode 618.

[0084] As shown in FIG. 1 1 , element C the shielding layer 620 (or another layer not shown) can include on and / or at least partially within itself a battery and / or a power source connector 624. The optical emitter 614 can attach to an external power supply via the power source connector 624 and / or can connect to the battery. The wearable patch 600 can also include a wireless transceiver or the like (not shown) to facilitate wireless communication with an external device (e.g., a smartphone, a tablet, a computer, or the like) comprising at least a non-transitory memory and a processor. The external device (not shown, also referred to as a remote device) can set at least a portion of the dose parameters of the PBM and / or electrical stimulation delivery. In some instances, the external device can include a camera and can determine a color of the patient’s skin from a picture and / or video and determine at least one dose parameter of the PBM based on the color (tone) the patient’s skin, because skin color (e.g., light to dark tones) has various effect on the absorption of different wavelengths of light. In another instance, the color of the patient’s skin can be entered into a prescription or dosage scheme for the PBM dose by a clinician.

[0085] FIG. 12 shows an illustration of an alternative wearable patch 700 that can be at least partially connected to the skin (e.g., by adhesive) and can include a hydrogel 706 between at least a portion of the wearable patch and the skin through which the PBM can be delivered. The wearable patch 700 can include a soft base 702 over at least the hydrogel 706 and a half-soft rim 704 on the sides of the soft base. The soft base 702 can be a flexible fabric like material that can move with skin and minimize any uncomfortable feeling. The half soft rim 704 can be at least partially stronger (and less flexible) than the soft base 702 and can elevate the soft base from directly touching the skin. The soft base 702 can include an opening for an optical emitter and / or an optical emitter (not shown, but similar to FIG. 11 ) for providing the PBM. The hydrogel 706 may include one or more analgesics or other active ingredients that do not block the light of the PBM. The hydrogel 706 can include one or more scattering medium for spreading the light of the PBM evenly across the skin surface and / or minimizing the height required by the wearable patch 700.

[0086] FIG. 13 shows an illustration of a strip 800 of wearable patches, from which a single wearable patch can be torn off and removed for use as prescribed / needed. Thestrip 800 is shown with four patches but can include any number one or greater (e.g., starts with two or more). Between each patch of the strip 800 a perforation 806 can separate the single wearable patches. Each perforation 806 can facilitate separating each of the patches. Each patch can include at least an opening 802 (and optionally an optical emitter that can emit through the opening) and at least one positive and negative electrical trace 804 (which may each include an electrode) to connect to a separate power supply. The strip 800 of wearable patches can be trimmable to fit one or more areas of the patient’s body.

[0087] FIG. 14 shows a block diagram of a system 900 for transcutaneously applying PBM to one or more target nerves. The system 900 can include a wearable 902 (e.g., a wearable patch, a wearable device, or the like), a control and power module 920, and, optionally, an external device 930. The wearable 902 can be in wired and / or wireless communication with the control and power module 920 and the control and power module can also be in wired and / or wireless communication with the external device 930. The wearable 902 can include at least optical emitter(s) 904 (one or more) for providing PBM to one or more target nerves through the skin and electrode(s) 906 (one or more) for providing electrical stimulation to the one or more target nerves through the skin. The wearable 902 can optionally include an adhesive module 908 and / or a connecting device (not shown, such as a securable band). The wearable 902 can include a battery and / or a power source connector 910 that can power at least the optical emitter(s) 904 and / or electrode(s) 906. The wearable 902 can in some instances include a temperature sensor 912 and / or a temperature management device 914, which may also be powered by the battery / power source connector 910. The temperature sensor 912 can be configured to sense a temperature of the skin at and / or near the wearable device (e.g., effected by the PBM and / or electrical stimulation). The temperature management device 914 can manage the temperature of the skin in response to the temperature sensed at the time. The temperature management device can be a cooling device and / or a switch to switch off the PBM and / or electrical stimulation in response to the sensed skin temperature breaching a predetermined safety threshold.

[0088] The control and power module 920 can include at least a non-transitory memory 922 and a processor 924, and may include a separate power source 926. The control and power module can determine and / or be used to program a dosage schedule and / or dose parameters for the PBM and / or electrical stimulation. While not shown, the control and power module 920 may also include a user interface and / or display for inputting information and / or displaying information and / or system alerts. The control and power module 920 can be programmed with PBM parameters and / or electrical stimulation parameters (e.g., based on a prescription) including, but not limited to, wavelength, max power, a parameter related to duty cycle (e.g., pulse width, frequency, etc.), duration, number of doses, the number of doses in a bolus, the wait time required between boluses before the wearable 902 can be active again. In some instances, the control and power module 920 can modulate and / or alter one of the PBM parameters and / or electrical stimulation parameters in response to a sensed parameter or identifying mark, such as nerve depth, skin tone, skin temperature, skin thickness, or the like. The control and power module 920 can receive sensed information from at least the electrode(s) 906, the temperature sensor 912, and the external device 930.

[0089] The external device 930 (e.g., smartphone, computer, tablet, or the like) can be a device of the patient, a caregiver, and / or a clinician. The external device 930 can include a controller 932 (with a non-transitory memory and processor, not shown), a user interface 934, and a display 936. The external device 930 can be used to communicate one or more dose parameters, prescriptions, or the like to the control and power module 920. The external device 930 may include one or more sensors, including a camera (not shown), and may be used to determine a patient’s skin tone or other visual skin information and send the skin tone or other visual skin information to the control and power module 920, where the control and power module can modulate one or more dose parameters based on the skin tone, other visual skin information, or the like. It should be understood that the one or more dose parameters may be modulated based on additional or alternative information.

[0090] Transcutaneous PBM (with or without electrical stimulation) can be applied to a plurality of areas of the body to at least partially block one or more target nerves including at least one sensory fiber that can conduct a signal related to pain,inflammation, arthritis, symptoms of arthritis, and / or heat hypersensitivity. It is known that PBM therapy can effectively block the small-diameter fibers (Ab and C) responsible for transmitting pain signals, while sparing the larger touch-associated fibers (A ). Although it is noted this has only been successful in achieving particularly effective pain relief with invasive methods for reaching the nerves. Not wishing to be bound by theory but the following are example locations and conditions that can be at least partially treated with transcutaneous PBM (optionally with electrical stimulation). For example, the atlanto occipital region can be a location to target the brainstem, spinal nuclei, and / or spinal cord regions. Potential pathologies that may be treated with PBM to one or more target nerves in the atlanto occipital region can include hypertension (including drug resistant hypertension, stroke symptoms, neurodegeneration of the brainstem, or the like. In other instances, activity of the rostral ventrolateral medulla (RVLM) can be reduced and cardiac disease associated with elevated RVLM can be treated (such as heart failure, hypertension, or the like). Alternatively, activity of the RVLM can be increased to treat patients with hemorrhagic or septic shock by elevating blood pressure.

[0091] In another example, sensory facial innervation can be used to reach branches of the trigeminal nerve that are largely superficial and PBM therapy for inhibiting at least one small fiber (optionally with electrical stimulation to excite at least one large fiber) can be delivered transcutaneously to locations on the path of the nerve (or related neural structures) including the foramen through which nerves come to the face before branching (such as the supraorbital, infraorbital, mental foramen, and supratrochlear ridge / groove). Silencing small fibers of facial nerves can treat headache types such as migraines, cluster headaches, etc., facial neuralgias due to injury and / or infection (e.g., herpetic neuralgia / shingles), or inflammation. In a further example, sites on the back of the head can be innervated by the greater occipital, lesser occipital, and auriculotemporal nerves and can be the target of transcutaneous PBM to treat headache and neuralgia of the posterior and superior head. As an example, in the lower extremities, foot and ankle pain can be treated by silencing small fibers of nerves such as the sural nerve, superficial peroneal nerve, saphenous nerve or the like. As an example, in the upper extremities, finger and hand pain (such as arthritis pain) can betreated by silencing small fibers of nerves such as the median and palmar ulnar nerves and / or radial and dorsal nerves or related neural structures.

[0092] As examples for arthritis treatment type systems, FIGS. 15-17 show wearable devices and at least part of an associated system for treating or at least partially preventing pain associated with osteoarthritis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, gout, or juvenile arthritis (including juvenile idiopathic arthritis) with transcutaneous PBM. FIG. 15 shows a wearable device 1000 for treating pain associated with arthritis. The wearable device 1000 can be, for example, a wristband or an ankle band. The wearable device 1000 can be secured to the wrist or ankle with a connector 1012, such as an elastic, a watchband like strap, or the like that can be tightened to the skin to keep the wearable device in place. The wearable device 1000 can include at least one optical emitter 1006 and at least one electrode 1004. In some instances (not shown) the wearable device can include the at least one optical emitter 1006 without the at least one electrode 1004. The at least one optical emitter 1006 can deliver a light therapy (PBM therapy) to one or more target nerves under the skin. The at least one electrode 1004 can provide an electrical stimulation to the one or more target nerves under the skin. The at least one electrode 1004 and the at least one optical emitter 1006 can be embodied in an electro-optical module (EOM) 1002 with a shared substrate / housing that can be made of shield material 1008 (e.g., can shield the surrounding area from at least one wavelength of the PBM) and a wearable device 1000 can be made of one or more EOMs 1002. As shown in FIG. 15, the wearable device 1000 can include a plurality of EOMs 1002 connected with a connector 1012 and each EOM can include an optical emitter 1006 flanked on opposing sides by an electrode 1004 (e.g., in a vertical stack electrode, optical emitter, electrode). In some instances, the EOMs 1002 can be links and comprise mechanical connections (not shown) to connect to each other to form the wearable device 1000 allowing the wearable device to be custom sized for a patient’s wrist / ankle. Each EOM 1002 can also include a temperature sensor and / or a temperature management device (e.g., individual Peltier modules) (both not shown) as discussed in more detail above. Each EOM 1002 may include a battery (not shown) and / or the wearable device 1000 may include a battery connected to each EOM.

[0093] The connector 1012 can additionally and / or alternatively provide pressure to at least the portion of each of the EOMs 1002 that includes the at least one optical emitter 1006 to the skin, such that the at least one optical emitter is pressed closer to the target nerves. Pressing the at least one optical emitter 1006 closer to the target nerves can reduce the amount of tissue intervening between the emitter and the target nerve (e.g., by displacing movable portions of the intervening tissue, stretching the tissues thinner, etc.). A wearable device 1000 that can be worn on a wrist, ankle, limb, or waist area can be adjusted (e.g., using an adjustable strap with a buckle, snap, etc.) to more effectively press the at least one optical emitter 1006 closer to the target nerves. It should be noted that a handheld device, such as described in detail above, can also be pressed closer to a nerve through force applied by the patient, medical professional or caregiver. FIG. 21 shows examples of a device including at least an optical emitter for providing PBM being pushed into the skin near the wrist (being manually pushed, but this should be understood to only be an example). Pushing the device into the skin lessens the distance between the optical emitter and the target nerve compared to if the device is not pressed into the skin. The left most figure shows the device not aligned with the target nerve and being moved to find the target nerve, the middle figure shows the device coming into alignment with the target nerve (and electrical stimulation being delivered to confirm the alignment), and the right most figure shows the PBM being applied to the pressed down skin (and other intervening tissues) above the target nerve.

[0094] FIG. 16 shows the wearable device 1000 in a system with a control and power module 1010 in wired and / or wireless communication with the wearable device. The control and power module 1010 can also, in some instances, be in wired and / or wireless communication with an external device 1020 (e.g., smartphone, tablet, computer, or the like) that can include at least a controller (memory and processor) (not shown), a display (not shown), and a user interface (not shown). The external device 1020 can communicate with the control and power module 1010 (e.g., send instructions, receive data, etc.). The control and power module 1010 can provide instructions and power to the at least one electrode 1004 and the at least one optical emitter 1006. The control and power module 1010 can instruct at least one electrode 1004 to provideelectrical stimulation to the one or more target nerves. In some instances, the control and power module 1004 can cycle through each of the at least one electrode 1004 (or pairs of electrodes) to determine which EOM(s) 1002 is / are nearest the one or more target nerves and optionally then to determine the distance(s) underneath the skin between the nearest EOM(s) and the one or more target nerves. The determinations by the control and power module 1010 can be based on stimulation thresholds (e.g., perception thresholds reported by the patient), impedance, and / or conduction readings from another recording system or at least one of the electrodes 1004 (the stimulating electrode and / or a paired sensing electrode). The control and power module 1010 and the at least one electrode 1004 can also determine when the at least one optical emitter is facing the skin of a wearer (so PBM is not inadvertently applied away from the skin, which may cause damage to at least the eyes if not shielded).

[0095] When the control and power module 1010 has determined the one or more EOMs 1002 is nearest the one or more target nerves, then the control and power module 1010 can instruct the optical emitter(s) 1006 in the one or more EOMs to emit light and provide light therapy in the form of PBM to the one or more target nerves through the skin. In some instances, the electrode(s) 1004 of the one or more EOMs 1002 can additionally provide electrical stimulation for additional therapeutic effect with the PBM. The PBM can at least partially block at least one small fiber in the one or more target nerves that can conduct at least pain sensation information (e.g., nociceptive pain information). The electrical stimulation can at least partially excite larger fibers in the one or more target nerves, which can disrupt pain processing, in addition to the at least one small fiber at least partially blocked by the PBM. The PBM and / or the electrical stimulation for therapeutic purposes can each have a dosing scheme set by a clinician (e.g., a prescription) and can each include at least one parameter that can be adjusted in response to one or more sensed feedback variables (e.g., distance to one or more target nerve, thickness of skin, skin tone, skin temperature, light reflectance, impedance, stimulation threshold, or the like). In one instance, not shown, the control and power module 1010 can include a light source and / or the EOMs 1002 can include light transmitting elements instead of optical emitters. For example, the light source ofthe control and power module 1010 can be connected to the light transmitting elements of the EOMs 1002 via a light pipe.

[0096] The control and power module 1010 can also have a number of other functions including, but not limited to those described now. The control and power module 1010 can steer a stimulation to each of the at least one electrode 1004 of the wearable device 1000 (e.g., to reach each of the one or more target nerves, find a better EOM 1002 to apply, for therapeutic purposes, or the like). The control and power module 1010 can adjust at least one parameter of the electrical stimulation in response to a feedback signal and / or manual input. The at least one parameter can include, but is not limited to, an electrode configuration, an amplitude, a pulse width, and / or a frequency. The control and power module 1010 can adjust at least one parameter of the light therapy (PBM therapy) in response to a feedback signal and / or a manual input. The at least one parameter of the light therapy (PBM therapy) can include, but is not limited to, location, power, and / or duration. The control and power module 1010 can also adjust thermal management of the wearable device when the wearable device 1000 includes at least one temperature sensor (not shown) that can sense skin temperature near the location(s) of the PBM and / or electrical stimulation and a thermal management device (not shown) that can make the adjustment when instructed by the control and power module.

[0097] FIG. 17 shows an alternative example of a system that can at least partially treat pain associated to arthritis where the wearable device comprises individual EOMs 1002 that can be connected to the skin of the user with an adhesive, pressure, suction, friction, or the like. While examples with the hands are shown any superficial nerves can be treated with these devices and / or systems. An EOM 1002 can be placed over the one or more target nerves (shown as two for illustration purposes). Each EOM 1002 can include, as discussed above at least one optical emitter 1006 and, optionally at least one electrode 1004 (shown as two electrodes and one optical emitter for illustration purposes). Each EOM 1002 can include a backing including a shield material 1008 that can block escape of at least one wavelength of the PBM (e.g., to protect the eyes the patient and / or eyes and / or skin of others in the vicinity, such as clinicians exposed to repetitive use). The EOM(s) 1002 can be positioned, for example, on a dorsal ulnarnerve, a radial nerve, a median nerve, and / or a palmar ulnar nerve. The EOM(s) 1002 can be positioned on more proximal portions of the one or more target nerves before the one or more target nerves branch. The EOM(s) 1002 can be connected wirelessly and / or with a wired connection to a control and power module 1010, which can also be connected wirelessly and / or with a wired connection to an external device 1020 (e.g., smartphone, computer, tablet or the like that can run control software). The EOM(s) 1002, control and power module 1010, and external device 1020 can have any of the functionality and / or structural features described above with respect to FIGS. 15 and 16 and may also have different / additional functionality. For instance, the at least one electrode 1004 can be used in concert with the control and power module 1010 to measure impedance to ensure contact of at least a desired EOM (e.g., EOM(s) over the target nerve(s)) with the skin.IV. Methods

[0098] Another aspect of the present disclosure can include methods 1 100, 1200, and 1300 (FIGS. 18-20) for transcutaneously delivering light signal(s) of photobiomodulation (PBM), and, additionally or alternatively, electrical stimulation, to one or more target nerves through a patient’s skin. PBM can be noninvasively and transcutaneously applied to one or more target nerves, each including at least one sensory fiber, under a patient’s skin via a handheld applicator, one or more wearable patches, a wearable device, or the like, or any combination thereof. PBM can be applied to treat and / or block nociceptive pain from a variety of sources, prevent or lessen the chronification of pain, treat pain associated with arthritis, treat or reduce neurogenic inflammation associated with arthritis or with pain or with other inflammatory disorder, or the like. The sensory fibers can be nociceptors and can conduct, for instance, signals related to pain, inflammation, arthritis, symptoms of arthritis, and / or heat hypersensitivity. Transcutaneous application of PBM can be preferable as it is a non- invasive treatment method and can in some instances be used outside a clinical environment, but requires additional considerations including, but not limited to, the need for appropriate shielding, proper placement of applicator devices on the skin over the target nerve or neural structure, determining and taking into account skin thickness,skin tone, skin temperature, distance to the one or more target nerves, light delivery schemes that address or manage one or more of these considerations, or the like.

[0099] Transcutaneous PBM can be applied to a plurality of areas of the body to at least partially block one or more target nerves including at least one sensory fiber that can conduct a signal related to pain, inflammation, arthritis, symptoms of arthritis, and / or heat hypersensitivity. It is known that PBM therapy can effectively block the smalldiameter fibers (Ab and C) responsible for transmitting pain signals, while sparing the larger touch-associated fibers (A|3). Although, it is noted this has only been able to successfully achieve a particularly strong effect with invasive methods for reaching the nerves. Not wishing to be bound by theory but the following are example locations and conditions that can be at least partially treated with transcutaneous PBM. Optionally, electrical stimulation (or another type of stimulation such as magnetic) can be applied in concert with the transcutaneous PBM to excite larger fibers to disrupt the processing of pain information in the central nervous system for additional effect. For example, the atlanto occipital region can be a location to target the brainstem, spinal nuclei, and / or spinal cord regions. Potential pathologies that may be treated with PBM to one or more target nerves in the atlanto occipital region can include hypertension (including drug resistant hypertension, stroke symptoms, neurodegeneration of the brainstem, or the like. In other instances, activity of the rostral ventrolateral medulla (RVLM) can be reduced and cardiac disease associated with elevated RVLM can be treated (such as heart failure, hypertension, or the like). Alternatively, activity of the RVLM can be increased to treat patients with hemorrhagic or septic shock by elevating blood pressure.

[0100] In another example, sensory facial innervation can be used to reach branches of the trigeminal nerve that are largely superficial and PBM therapy (optionally with electrical stimulation) can be delivered transcutaneously to locations on the path of the nerve (or related neural structures) including the foramen through which nerves come to the face before branching (such as the supraorbital, infraorbital, mental foramen, and supratrochlear ridge / groove). Silencing small fibers of facial nerves can treat headache types such as migraines, cluster headaches, etc., facial neuralgias due to injury and / or infection (e.g., herpetic neuralgia / shingles), or inflammation. In a furtherexample, sites on the back of the head can be innervated with transcutaneous PBM by the greater occipital, lesser occipital, and auriculotemporal nerves to treat headache and neuralgia of the posterior and superior head. As an example, in the lower extremities, foot and ankle pain can be treated by silencing small fibers of nerves such as the sural nerve, superficial peroneal nerve, tibial nerve, saphenous nerve or the like. As an example, in the upper extremities, finger and hand pain (such as arthritis pain) can be treated by silencing small fibers of nerves such as the median and palmar ulnar nerves.

[0101] For purposes of simplicity, the methods 1100, 1200, and 1300 are shown and described as being executed serially; however, it is to be understood and appreciated that the present disclosure is not limited by the illustrated order as some steps could occur in different orders and / or concurrently with other steps shown and described herein. Moreover, not all illustrated aspects may be required to implement the method, nor is the method necessarily limited to the illustrated aspects.

[0102] Referring now to FIG. 18, illustrated is a method 1100 for transcutaneous application of PBM to one or more target nerves under the skin to at least partially block at least one small fiber conducting sensory information in one or more target nerves. The one or more target nerves can each include, but are not limited to, at least one sensory fiber related to pain, inflammation, arthritis, symptoms of arthritis, and / or heat hypersensitivity. The method 1100 can be performed with a system comprising at least a processor and a memory, such as one of the controllers, control and power modules, and / or external devices connected with the PBM application devices described with respect to FIGS. 1 -17. At 1102 a location of one or more target nerves under skin of a patient can be identified based on at least one identifying parameter (e.g., temperature, conductivity, landmark, etc.) provided by a target locating system and / or input according to instructions and / or inputs (e.g., self-reporting of a stimulation response, etc.) from the patient. The target locating system can, in some instance, record the at least one identifying parameter related to the one or more target nerves under the skin of the patient and / or the instructions and / or inputs from the patient. The target locating system, can for example include one or more imaging devices and / or electrical stimulation devices that can locate a target location on the skin above the one or more targetnerves. Imaging devices can include, but are not limited, to an optical coherence tomography (OCT) system, an ultrasound system, a magnetic resonance (MR) neurography system, a positron emission tomography (PET) or other radiotracer imaging system. Electrical stimulation devices can include at least one stimulating electrode, and optionally a recording electrode to sense at least one electrical parameter of the one or more target nerve.

[0103] The system can identify the location based on analysis of the image and / or the sensed at least one electrical parameter, or patient self-report of paresthesia or nerve block. In some instances, an identifying mark can be placed on, in, and / or under the skin to mark the location. The identifying mark can be, but is not limited to, a tattoo, an implanted or external radio frequency identification device, a series of implanted quantum dot codes, or the like. For example, the tattoo may be a dot the color of a freckle or a dye that is not visible to the human eye in daylight (or at all) but is detectable by the PBM application device or is visible under UV light. In the latter case, the PBM application device can additionally deliver a low amount of UV light to visualize the tattoo for correctly positioning the system for PBM delivery. In another instance, the imaging device and / or electrical stimulation device can be embodied with the PBM application device such that the combination device need not be moved to provide the PBM to the identified location.

[0104] Optionally, at 1 104 a depth of the one or more target nerves under the skin can be estimated based on the at least one identifying parameter or another parameter. For instance, the depth of the one or more target nerves can be determined by optical imaging if sufficiently superficial (as would be known in the art for each of the imaging modalities described above). In another example, electrical stimulation could be used to excite the one or more target nerves and the depth can be estimated based on the stimulation threshold. The system can use the stimulation threshold of the electrical stimulation to estimate the distance and then estimate the dose of PBM and / or one or more dose parameters to achieve the desired therapeutic effect based on the estimated distance and / or the stimulation threshold directly. In some instances electrical stimulation of the one or more target nerves can be confirmed by at least one of patient self-reporting paresthesia and the extent of the paresthesia’s distribution, recordings bya recording electrode (e.g., as commonly used for a nerve conduction test), a visible motor responses (if the one or more target nerves comprise mixed fibers), and / or a recorded motor response using electromyography (EMG) (if the one or more target nerves comprise mixed fibers).

[0105] At 1 106 dose parameters can be configured (e.g., by the processor) for a dose of PBM to be applied through the skin to modify conduction in the at least one sensory fiber related to pain based on the location and / or the depth of the one or more target nerves. The dose parameters can be configured based on one or more predetermined models, a look up table, or the like. The one or more models can account for skin tone information, skin thickness, depth of the one or more target nerves, the prescription for the PBM, or the like. In one example, a single system can estimate dose delivery and can provide graphical information (e.g., through a display of the controller and / or in communication with the controller) to the clinician or other user about light that can be delivered / is being delivered to the tissue. Examples of such information can include the trajectory of the light emission axis of the optical emitter(s), dose information (e.g., as contours), a selected target, recommended wavelength, time, power, or the like, and / or expected outputs such as days to reduced transmission, description of reduced transmission as a function of time or the like. In some instances, a clinician can use the system with the controller to keep records and / or automate dose estimation and recommendations.

[0106] At 1 108 the dose of PBM can be sent to the PBM application device that can deliver the dose of PBM with the dose parameters through the patient’s skin to the one or more target nerves. The PBM can be delivered to have a therapeutic effect (e.g., at least partially treat and / or stop conduction of a pain signal). In some instances, electrical stimulation can be applied concurrently or consecutively with the PBM to add on to the therapeutic effect. In other instances, the PBM can be applied for diagnostic purposes, such as to determine if another more invasive type of nerve block would be appropriate for a patient, to determine conduction information of the one or more target nerves, or the like. In one example, after the dose of PBM is applied a condition suffered by the patient can be diagnosed based on the effect caused by the dose of PBM. The one or more target nerves can be in an Atlanto occipital region of thepatient’s brain, in the patient’s face or on a portion of the patient’s head, a trigeminal nerve, an occipital nerve, a nerve in the foot or ankle (such as a tibial nerve), and / or a nerve in the wrist and / or hand (such as a median or ulnar nerve).

[0107] Prior to delivery of the PBM a shield can be positioned to block escape of at least one wavelength of the dose of PBM. The shield can be any material and / or configuration with this function (e.g., hard, soft, movable, adhesive, etc.) as discussed above with respect to FIGS. 1 -17. FIG. 19 illustrates a method 1200 for positioning a PBM delivery device with a shield to transcutaneously apply PBM. At 1202 the device for applying the PBM (e.g., handheld applicator, patch, wearable device, or the like) can be positioned on or above the skin of the patient at the location of the nerve. The location can be determined as described above with respect to at least FIG. 18. The position can be “locked” through the use of an adhesive, pressure, suction, friction, or the like. At 1204 the system can check if the shield is positioned properly to block the escape of errant light from the PBM application. For instance, the shield can include one or more sensors or electrodes at the shield - skin interface that can detect if the shield is in contact with the skin (e.g., to protect at least the eyes of the patient and others in the vicinity). The one or more sensors can include, but are not limited to a pressure sensor, an impedance sensor, or the like. In some instances, the electrode(s) for determining the location of the one or more target nerves, estimating the depth of the one or more target nerves, and / or providing electrical stimulation can sense the position of the shield.

[0108] The system (e.g., the processor connected with the PBM delivery device) can determine if the shield is positioned correctly at a time based on information received from the one or more sensors or electrodes (e.g., based on predetermined thresholds). If the shield is not determined to be positioned properly the system can alert the user (e.g., patient, caregiver, and / or clinician) via a display, light, sound, or the like (on the device, an external device in communication, or the like). If the shield is not positioned correctly the processor can prevent and / or stop (if light was being provided) the PBM until the shield is positioned correctly again. At 1206 the shield can be repositioned (this can occur as many times as necessary). At 1208, the delivery devicecan provide PBM to the one or more target nerves through the skin if the shield is determined to be positioned properly.

[0109] Referring now to FIG. 20, illustrated is a method 1300 for controlling a PBM delivery device for optimal dosage delivery and / or safety. The method 1300 can be particularly useful with a take home device used without the presence of a clinician. At 1302 the device and / or system comprising at least a processor can determine if the optical emitter for delivering the PBM is facing the skin. This can be a safety measure so the PBM cannot be started if the device is not even facing the skin (e.g., no light accidently applied directly to the eyes). This can be determined with at least one sensor that can measure pressure, reflectance, impedance, proximity, or the like and send the measured data to the processor to compare with known values for when the optical emitter is facing the skin. At 1304 a location and / or locations of the one or more target nerves can be tested (e.g., with electrical stimulation and / or short bursts of stimulatory light) prior to delivering the light (PBM) therapy via the at least one emitter. Testing the locations of the one or more target nerves may additionally provide feedback information (e.g., skin thickness, skin tone, depth of the one or more target nerves, or the like). In response to the testing and / or receiving any other feedback information (e.g., from one or more sensors or manual input) the system may perform a number of functions related to applying the PBM in an optimal dosage delivery and safe manner.

[0110] For example, if the PBM delivery device includes at least one electrode (in the manners described above with respect to FIGS. 1 -17) then at 1306 stimulation can be steered to each of the at least one electrode (e.g., to reach each of the one or more target nerves, find the best location to apply therapy (PBM and / or electrical stimulation), for therapeutic purposes, or the like). At 1308 at least one parameter of the electrical stimulation can be adjusted in response to a feedback signal and / or manual input. The at least one parameter can include, but is not limited to, an electrode configuration, an amplitude, a pulse width, and / or a frequency. At 1310 at least one parameter of the light therapy (PBM therapy) can be adjusted in response to a feedback signal and / or a manual input. The at least one parameter of the light therapy (PBM therapy) can include, but is not limited to, location, power, and / or duration. Any adjustments can be within safety limits hard coded in a system or pre-programmed by a clinician. If thedevice includes a temperature sensor and / or temperature management device, then at 1312 thermal management of the device can be adjusted. A temperatures sensor can sense skin temperature near the location(s) of the PBM and / or electrical stimulation and a thermal management device (not shown) that can make the adjustment if the skin temperature is too high (e.g., above a predetermined threshold. The PBM delivery can also be stopped if the skin temperature is above a predetermined threshold.

[0111] From the above description, those skilled in the art will perceive improvements, changes, and modifications. Such improvements, changes and modifications are within the skill of one in the art and are intended to be covered by the appended claims.

Claims

The following is claimed:1 . A system comprising: a PBM delivery system comprising: an optical emitter configured to deliver a dose of PBM with parameters for the dose of PBM through a location on a patient’s skin to one or more target nerves, and a shield configured to extend outward around at least a portion of the optical emitter and configured to block escape of at least a wavelength of the dose of PBM.

2. The system of claim 1 , further comprising: a target locating system comprising: a querying device configured to test various locations for at least one identifying parameter indicative of at least one target nerve; and a recording device configured to locate the one or more target nerves under skin of a patient, wherein the one or more target nerves each comprise at least one sensory fiber.

3. The system of claim 2, wherein the sensory fiber conducts signals related to pain, inflammation, arthritis, symptoms of arthritis, and / or heat hypersensitivity.

4. The system of claim 2, further comprising a controller comprising: a non-transitory memory storing instructions, and a processor configured to execute the instructions to: identify a location of the one or more target nerves based on the at least one identifying parameter, and / or estimate a depth of the one or more target nerves under the patient’s skin based on the at least one identifying parameter, andconfigure the dose parameters for the dose of PBM to be applied to modify conduction in the at least one sensory fiber related to pain based on the location and / or the depth of the one or more target nerves, wherein the dose parameters comprise at least one or more of a power, a wavelength, a frequency, and a duration.

5. The system of claim 4, wherein the controller operates in real time for detection of the location of the one or more target nerves and / or the depth of the one or more target nerves and configuration of the dose parameters of the PBM delivery.

6. The system of claim 4, wherein at least a portion of the controller is within the target locating system and is configured to record the at least one identifying parameter related to the one or more target nerves under the patient’s skin.

7. The system of claim 6, wherein the processor is further configured to execute instructions to calibrate the dose of PBM such that the at least one identifying parameter is further determined based on the patient’s skin tone.

8. The system of claim 2, wherein at least a portion of the target locating system and at least a portion of the PBM delivery system are embodied as a single device.

9. The system of claim 2, wherein the target locating system comprises an imaging wand configured to be moved over a target area to record an image comprising the one or more target nerves.

10. The system of claim 9, wherein the imaging wand is used for at least one of optical coherence tomography, magnetic resonance neurography, positron emission tomography, radiotracer imaging, or ultrasound.1 1 . The system of claim 2, wherein the PBM delivery system is removably coupled to the target locating system.

12. The system of claim 2, wherein the target locating system comprises an electrical stimulation device comprising at least one electrode configured to electrically stimulate the one or more target nerves through the patient’s skin.

13. The system of claim 12, wherein the target locating system comprises at least one electrode configured to sense a stimulation of the one or more target nerves under the patient’s skin.

14. The system of claim 12, wherein the processor is configured to estimate a distance from a surface of the patient’s skin to the one or more target nerves based on at least one stimulation threshold.

15. The system of claim 12, wherein the at least one electrode configured for stimulation is substantially annular and the system further comprises a lumen having an opening extending in the approximate center of the substantially annular at least one electrode and connected to the optical emitter to provide the PBM dose to the one or more target nerves through the patient’s skin.

16. The system of claim 12, wherein the electrical stimulation device is configured to detect whether the system is in sufficient contact with the patient’s skin, wherein the processor stops or refuses to instruct the PBM delivery system to deliver the dose of PBM when at least a portion of the system is not in sufficient contact with the patient’s skin.

17. The system of claim 12, wherein the at least one electrode configured for stimulation is further configured to provide electrical stimulation concurrent with delivery of the dose of PBM for therapeutic purposes.

18. The system of claim 2, wherein the target locating system comprises a wand and the PBM delivery system is within the target locating system such that the wand is at least a portion of the shield.

19. The system of claim 2, wherein a location on the patient’s skin indicative of a target area is marked on and / or under the patient’s skin by an identifying mark.

20. The system of claim 19, wherein the identifying mark comprises a tattoo, an implanted or external radio frequency identification device, and / or a series of implanted quantum dot codes.21 . The system of claim 19, further comprising a camera configured to detect the identifying mark and send information related to the identifying mark to the processor, and the processor is further configured to process the information related to the identifying mark.

22. The system of claim 1 , wherein the optical emitter comprises a light source coupled to a fiber optic cable.

23. The system of claim 1 , wherein the system comprises at least one battery configured to power at least the optical emitter.

24. The system of claim 1 , wherein the parameters comprise at least a wavelength from 400 nm to 1200 nm.

25. The system of claim 1 , configured to deliver the dose of PBM again at a later time.

26. The system of claim 1 , further comprising a controller configured to implement at least one dose management element.

27. The system of claim 26, wherein the at least one dose management element allows the PBM to be administered as boluses configured by a clinician and deliverable by the optical emitter.

28. The system of claim 1 , wherein an orientation of the optical emitter along the one or more nerves affects an amount of conduction blocked in the one or more nerves.

29. The system of claim 1 , wherein the optical emitter extends in an orientation perpendicular to the one or more nerves to increase a likelihood of the PBM being directed at the one or more nerves.

30. The system of claim 1 , wherein the optical emitter extends in an orientation perpendicular to the one or more nerves to deliver the PBM to multiple nerves simultaneously.31 . A wearable patch comprising: a skin-side layer comprising: an adhesive portion configured to attach to a patient’s skin, and at least one opening or window configured to facilitate transmission of a dose of PBM having dose parameters through the skin of the patient to at least one nerve to modify conduction in at least one sensory fiber related to pain, inflammation, arthritis, symptoms of arthritis, and / or heat hypersensitivity; and at least one layer configured to block escape of at least the wavelength of the dose of PBM.

32. The wearable patch of claim 31 , further comprising an optical emitter positioned relative to the opening or window such that the dose of PBM travels out the opening towards the skin of the patient.

33. The wearable patch of claim 32, wherein the optical emitter is configured to attach to an external power supply.

34. The wearable patch of claim 32, wherein a battery is within and / or on the exterior-side layer to power the optical emitter.

35. The wearable patch of claim 32, further comprising an optical fiber coupled to an optical emitter and configured to extend into or through the opening or window to deliver the dose of PBM.

36. The wearable patch of claim 31 , further comprising a hydrogel layer at least between the opening or window and the skin, wherein the dose of PBM is emitted through the opening or window.

37. The wearable patch of claim 31 , wherein the patch is removeable.

38. The wearable patch of claim 31 , wherein the adhesive portion and / or the opening is configured to facilitate delivery of an analgesic in concert with the dose of PBM.

39. The wearable patch of claim 31 , wherein the skin-side layer further comprises at least two electrodes.

40. The wearable patch of claim 39, wherein the at least two electrodes are configured to identify and / or confirm a location and / or a depth of the at least one nerve and / or to ensure attachment of the wearable patch to the patient’s skin.41 . The wearable patch of claim 39, wherein the at least two electrodes are configured to deliver a stimulation concurrently and / or consecutively with the delivery of the PBM.

42. The wearable patch of claim 39, wherein at least a portion of the dose parameters are set by a remote device.

43. The wearable patch of claim 42, wherein the remote device comprises: a camera configured to receive input related to a color of the patient’s skin; and a controller in communication with the camera that is configured to determine the color of the patient’s skin, wherein the dose parameters are determined based on the color of the patient’s skin.

44. The wearable patch of claim 42, wherein the dose parameters are determined based on a color of the patient’s skin entered by a clinician.

45. The wearable patch of claim 31 , configured to be separated from a strip of a plurality of separable wearable patches.

46. A method comprising: identifying, by a system comprising a processor, a location of one or more target nerves under skin of a patient based on at least one identifying parameter provided by a target locating system and / or input according to instructions from the patient, wherein the one or more target nerves each comprise at least one sensory fiber related to pain, inflammation, arthritis, symptoms of arthritis, and / or heat hypersensitivity; configuring, by the system, dose parameters for a dose of PBM to be applied through the skin to modify conduction in the at least one sensory fiber related to pain based on the location of the one or more target nerves; and sending, by the system, the dose of PBM to a PBM delivery system configured to deliver the dose of PBM with the dose parameters through the patient’s skin to the one or more target nerves.

47. The method of claim 46, wherein a shield is positioned to block escape of at least the wavelength of the dose of PBM.

48. The method of claim 46, further comprising, after the dose of PBM is delivered, determining, by the system, whether another type of nerve block would block conduction in the one or more nerves.

49. The method of claim 46, further comprising, after the dose is delivered, diagnosing, by the system, a condition suffered by the patient based at least in part on an effect caused by the dose of PBM.

50. The method of claim 46, wherein at least one of the identifying, estimating, and configuring is done based on at least one predetermined model.51 . The method of claim 46, further comprising displaying, by the system, graphical information about light delivered to the tissue, wherein the information includes a trajectory of a light emission axis for the PBM dose, dose delivery information, and at least one recommendation for future treatments.

52. The method of claim 46, wherein the target locating system is configured to record the at least one identifying parameter related to the one or more target nerves under the skin of the patient.

53. The method of claim 46, wherein the one or more target nerves is in an Atlanto occipital region of the patient’s brain.

54. The method of claim 46, wherein the one or more target nerves is in the patient’s face or on a portion of the patient’s head.

55. The method of claim 54, wherein the one or more target nerves is a trigeminal nerve.

56. The method of claim 54, wherein the one or more target nerves is an occipital nerve.

57. The method of claim 46, wherein the one or more target nerves is superficial.

58. The method of claim 46, wherein the one or more target nerves is in the patient’s foot or ankle.

59. The method of claim 46, wherein the one or more target nerves is in the patient’s hand or wrist.

60. The method of claim 46, wherein the one or more target nerves is a tibial nerve.61 . The method of claim 46, wherein the one or more target nerves is a median nerve and / or an ulnar nerve.

62. The method of claim 46, further comprising: estimating, by the system, a depth of the one or more target nerves under the skin based on the at least one identifying parameter, and further configuring, by the system, the dose parameters for the dose of PBM to be applied through the skin to modify conduction in the at least one sensory fiber related to pain based on the depth of the one or more target nerves.

63. A system comprising: a wearable device for treating pain associated with arthritis, the wearable device comprising: at least one optical emitter configured to deliver a light therapy to one or more target nerves, and at least one electrode configured to provide a stimulation; and a control and power module in communication with the wearable device.

64. The system of claim 63, wherein the arthritis is an osteoarthritis, a rheumatoid arthritis, a psoriatic arthritis, or an idiopathic arthritis.

65. The system of claim 63, wherein the system further comprises an external device comprising at least a controller and a user interface, wherein the external device is configured to communicate with the control and power module.

66. The system of claim 63, wherein the wearable device is a wrist and / or an ankle band.

67. The system of claim 66, wherein the wrist and / or ankle band comprises a plurality of link modules, where each link module comprises one or more of each of the at least one electrode and the at least one optical emitter.

68. The system of claim 63, wherein the control and power module and the at least one electrode are configured to: determine the at least one optical emitter is facing the skin of a wearer, and / or test a location of the one or more target nerves prior to the at least one optical emitter delivering the light therapy.

69. The system of claim 63, wherein the wearable device further comprises a temperature sensor and a temperature management device.

70. The system of claim 63, wherein the control and power module is configured to: steer a stimulation to each of the at least one electrode of the wearable device; adjust at least one parameter of the stimulation, wherein the at least one parameter comprises an electrode configuration, an amplitude, a pulse width, a frequency; adjust at least one parameter of the light therapy, wherein the at least one parameter of the light therapy comprises location, power, and / or duration; and / or adjust thermal management of the wearable device.71 . The system of claim 63, wherein the wearable device comprises at least one adhesive module comprising the at least one electrode and the at least one optical emitter, wherein the at least one adhesive module is configured to be placed over the one or more target nerves.

72. The system of claim 63, wherein the wearable device comprises a connector configured to secure at least the at least one optical emitter close to skin and the one or more target nerves with a pressure configured to shorten the distance and / or lessen an amount of intervening tissue between the at least one optical emitter and the one or more target nerves.

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