Non-invasive magnetic or electrical nerve stimulation to treat gastroparesis, functional dyspepsia, and other functional gastrointestinal disorders

Abstract

Devices, systems and methods are disclosed for treating or preventing gastroparesis, functional dyspepsia, and other functional gastrointestinal disorders. The methods comprise transmitting impulses of energy non-invasively to selected nerve fibers, particularly those in a vagus nerve. The methods provide damaged interstitial cells of Cajal (ICC) with trophic factors via vagal afferent nerve fibers, thereby reversing ICC damage, and as a consequence improving gastric motility. The methods also increase levels of inhibitory neurotransmitters in the brain so as to decrease neural activity within the area postrema, or they deactivate a resting state neural network containing parts of the anterior insula and anterior cingulate cortex, which will thereby reduce abnormal interoception and visceral hypersensitivity.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]The present application is a Continuation in Part of: (1) U.S. Nonprovisional application Ser. No. 13 / 222,087 filed Aug. 31, 2011; (2) U.S. Nonprovisional application Ser. No. 13 / 183,765 filed Jul. 15, 2011, which claims the benefit of U.S. Provisional Application No. 61 / 488,208 filed May 20, 2011; and (3) U.S. Nonprovisional application Ser. No. 13 / 075,746 filed Mar. 30, 2011, which claims the benefit of U.S. Provisional Application 61 / 451,259 filed Mar. 10, 2011; each of which is incorporated herein by reference in its entirety.BACKGROUND OF THE INVENTION [0002]The field of the present invention relates to the delivery of energy impulses (and / or fields) to bodily tissues for therapeutic purposes. The invention relates more specifically to devices and methods for treating conditions associated with gastroparesis, functional dyspepsia, and functional gastrointestinal disorders generally. The energy impulses (and / or fields) that are used t...

AI Technical Summary

Benefits of technology

[0036]Injury or loss of interstitial cells of Cajal (ICC) is the single most common pathophysiological feature found in patients with gastroparesis and other motility disorders of the gastrointestinal system. The ICC injury or loss may be due to a deficiency of trophic factors necessary for normal ICC maturation and survival. The present invention provides requisite trophic factors to gastric ICC cells and their progenitors, through electrical stimulation of a vagus nerve. In particular, it provides trophic factors to the ICC that are associated with intramuscular arrays, which are mechanoreceptors that are connected to vagus afferent nerve fibers. A method of the invention involves electrical stimulation of vagus afferent nerve fibers so as to imitate afferent signals that would have been transmitted by the vagal afferents in a normal individual. According to the invention, the afferent vagus nerve fiber will respond by providing to the damaged ICC what would have been the normal trophic factors, thereby reversing ICC degradation or loss, and as a consequence improving gastric motility.

[0044]A source of power supplies a pulse of electric charge to the electrodes or magnetic stimulator coil, such that the electrodes or magnetic stimulator produce an electric current and / or an electric field within the patient. The electrical or magnetic stimulator is configured to induce a peak pulse voltage sufficient to produce an electric field in the vicinity of a nerve such as a vagus nerve, to cause the nerve to depolarize and reach a threshold for action potential propagation. By way of example, the threshold electric field for stimulation of the nerve may be about 8 V / m at 1000 Hz. For example, the device may produce an electric field within the patient of about 10 to 600 V / m (preferably less than 100 V / m) and an electrical field gradient of greater than 2 V / m / mm. Electric fields that are produced at the vagus nerve are generally sufficient to excite all myelinated A and B fibers, but not necessarily the unmyelinated C fibers. However, by using a reduced amplitude of stimulation, excitation of A-delta and B fibers may also be avoided.

[0045]The preferred stimulator shapes an elongated electric field of effect that can be oriented parallel to a long nerve, such as a vagus. By selecting a suitable waveform to stimulate the nerve, along with suitable parameters such as current, voltage, pulse width, pulses per burst, inter-burst interval, etc., the stimulator produces a correspondingly selective physiological response in an individual patient. Such a suitable waveform and parameters are simultaneously selected to avoid substantially stimulating nerves and tissue other than the target nerve, particularly avoiding the stimulation of nerves in the skin that produce pain.

Problems solved by technology

The electrical circuits for magnetic stimulators are generally complex and expensive and use a high current impulse generator that may produce discharge currents of 5,000 amps or more, which is passed through the stimulator coil to produce a magnetic pulse.

Non-invasive procedures are generally painless and may be performed without the dangers and costs of surgery.

A difficulty in interpreting the epidemiological data mentioned above is that considerable symptomatic and pathophysiological overlap exists between FDIG disorders.

No drugs with established efficacy are definitive for treatment of functional dyspepsia and gastroparesis.

Low-frequency / high-energy GES appears to work well in principle, but it is not presently suitable for routine clinical use.

High-frequency / low-energy GES does not significantly modify gastric slow wave and motor activity and does not appear to consistently resolve the problem of delayed gastric emptying, but may it nevertheless resolve some symptoms.

However, because these methods are intended to treat morning sickness, side-effects of chemotherapy, etc., they are not designed specifically for treating for the forms of nausea and vomiting that are due to dyspepsia, gastroparesis, or other functional gastrointestinal disorders and do not simultaneously treat other symptoms of those disorders such as bloating.