Devices, Systems and Methods for Treating Urological and Gastrointestinal Disorders by Electrical Stimulation of the Foot

Abstract

Provided herein are devices, systems, and methods for treating urological and gastrointestinal disorders, including bedwetting, through stimulation of the dorsal or plantar surface of the foot, including the superficial peroneal nerve and branches thereof, such as the dorsal intermediate and medial cutaneous nerves, or the medial and/or and lateral plantar nerves. The device facilitates placement of electrodes on the foot. Also provided herein is a system including the device, a pulse generator, and a controller, and methods of manufacturing and using the same.

1 . An electrode-containing device comprising either:
 a. a base adapted to cover a portion of a plantar surface of a human foot including a portion of the forefoot overlaying a plurality of branches of the medial or lateral plantar nerves and a portion of the hindfoot overlaying the medial and lateral plantar nerves; a first electrode attached to the base at a position adapted to the hindfoot to contact skin overlaying the medial and lateral plantar nerves; a second electrode attached to the base at a position adapted to the forefoot to contact skin overlaying a plurality of branches of the medial or lateral plantar nerves in the forefoot; and a first and second electrical lead attached to the first and second electrodes, respectively, or   b. a base adapted to cover a portion of a dorsal surface of a human foot including a portion of the forefoot overlaying a plurality of branches of the dorsal intermediate and medial cutaneous nerves, deep peroneal nerve, sural nerve, and/or saphenous nerve, and a portion of the hindfoot overlaying the superficial peroneal nerve, deep peroneal nerve, and/or saphenous nerve; a first electrode attached to the base at a position adapted to a dorsal portion of the hindfoot to contact skin overlaying the superficial peroneal nerve, deep peroneal nerve, and/or saphenous nerve; a second electrode attached to the base at a position adapted to a dorsal portion of the forefoot to contact skin overlaying a plurality of branches of the dorsal intermediate and medial cutaneous nerves, deep peroneal nerve, sural nerve, and/or saphenous nerve in the forefoot; and a first and second electrical lead attached to the first and second electrodes, respectively.   
     
     
         2 . The electrode-containing device of  claim 1 , in which the first electrode is a cathode and the second electrode is an anode, or wherein the first electrode is an anode and the second electrode is a cathode. 
     
     
         3 . The electrode-containing device of  claim 2 , in which the first electrode or the second electrode overlays at least 50% of the width of the sole at the forefoot. 
     
     
         4 . The electrode-containing device of  claim 2 , in which the first electrode or the second electrode overlays at least a portion of the metatarsophalangeal joint. 
     
     
         5 . The electrode-containing device of  claim 2 , in which the first electrode or the second electrode overlays at least a portion of the calcaneus bone. 
     
     
         6 . The electrode-containing device of  claim 2 , in which the first electrode or the second electrode overlays a predominance of branches of the medial and lateral plantar nerves in the forefoot. 
     
     
         7 . The electrode-containing device of  claim 1 , wherein the base has a perimeter having the shape of a sole of a foot, and optionally is an orthotic insert, or wherein the base has a perimeter having the shape of the dorsal area of a foot from the proximal phalanges to the talocrural joint. 
     
     
         8 . The electrode-containing device of  claim 1 , wherein the base is a thin polymeric film having an adhesive on a side comprising the electrodes and facing the foot. 
     
     
         9 . The electrode-containing device of  claim 1 , further comprising one or more connectors for an external pulse generator attached to the leads. 
     
     
         10 . The electrode-containing device of  claim 1 , further comprising an adhesive on a surface of the base and/or electrodes for removably securing the device to a patient's foot. 
     
     
         11 . The electrode-containing device of  claim 1 , wherein the base is shaped substantially like a plantar surface or sole of a human foot, or wherein the base is shaped substantially to interact with the dorsal surface of a human foot. 
     
     
         12 . An electrical nerve stimulation system comprising:
 an electrode-containing device as claimed in  claim 1 ;   a fixed output pulse generator external to the electrode-containing device and connected to the leads, configured to generate monophasic, rectangular, or biphasic pulses of pulsewidth 0.01-3 ms between 1-100 V and 1-80 mA, at frequency 1-50 Hz.   
     
     
         13 . (canceled) 
     
     
         14 . (canceled) 
     
     
         15 . The system of  claim 12 , wherein the pulse generator provides pulses having a pulsewidth of 0.2 ms at 5 Hz, and wherein the intensity of the pulses is from 2-6 times a toe twitch threshold of a patient. 
     
     
         16 . (canceled) 
     
     
         17 . A method of treating urological or gastrointestinal disorders comprising:
 applying an electrode-containing device as claimed in  claim 1  to a foot of a patient in need of such treatment, wherein the electrode-containing device is attached to a pulse generator external to the electrode-containing device comprising a connector for connecting the pulse generator to the device;   stimulating the patient's foot with the device with pulses of pulsewidth 0.01-3 ms between 1-100 V and 1-100 mA, at frequency 1-50 Hz, thereby stimulating either the lateral and/or medial plantar nerves or the dorsal intermediate and medial cutaneous nerves, deep peroneal nerve, sural nerve, and/or saphenous nerves of the patient; and   optionally administering to the patient one or more of:   an anti-muscarinic compound;   a serotonin reuptake inhibitor;   a serotonin receptor antagonist; and   an opioid drug.   
     
     
         18 . The method of  claim 17 , in which the urological or gastrointestinal disorder is one or more of: overactive bladder (OAB) symptoms including bladder overactivity, urinary frequency, urinary urgency, urinary incontinence; interstitial cystitis (IC); urinary retention; pelvic pain; fecal incontinence; irritable bowel syndrome (IBS); and constipation. 
     
     
         19 . (canceled) 
     
     
         20 . The method of  claim 18 , in which the urinary incontinence is bedwetting, and wherein the device delivers pulses of a frequency of 5 Hz, 0.2 ms pulsewidth, and wherein the intensity of the pulse is from 2-6 times a toe twitch threshold of a patient. 
     
     
         21 . The method of  claim 17 , wherein the patient's foot is stimulated for from 1 to 360 minutes. 
     
     
         22 . (canceled) 
     
     
         23 . (canceled) 
     
     
         24 . The method of  claim 17 , further comprising administering an anti-muscarinic compound to the patient, wherein the anti-muscarinic compound is selected from the group consisting of atropine, benztropine, biperiden, ipratropium, oxitropium, tiotropium, glycopyrrolate, oxybutynin, tolterodine, chlorpheniramine, diphenhydramine, dimenhydrinate, orphenadrine, trihexyphenidyl, and dicyclomine. 
     
     
         25 . (canceled) 
     
     
         26 . (canceled) 
     
     
         27 . (canceled) 
     
     
         28 . The method of  claim 17 , further comprising administering to a patient in need thereof a serotonin reuptake inhibitor and/or a serotonin receptor antagonist, wherein the serotonin reuptake inhibitor is selected from the group consisting of alaproclate, citalopram, dapoxetine, escitalopram, femoxetine, fluoxetine, fluvoxamine, ifoxetine, indalpine, omiloxetine, panuramine, paroxetine, pirandamine, duloxetine, dapoxetine, sertraline, and zimelidine and the serotonin receptor antagonist is selected from the group consisting of alprenolol, AV-965, BMY-7,378, cyanopindolol, dotarizine, flopropione, GR-46,611, isodocyanopindolol, isamoltane, lecozotan, methiothepin, methysergide, MPPF, NAN-190, oxprenolol, pindobind, pindolol, propranolol, risperidone, robalzotan, SB-649,915 (which acts as both a reuptake inhibitor and a receptor antagonist), SDZ-216,525, spiperone, spiramide, spiroxatrine, UH-301, WAY100135, WAY 100635, and xylamidine. 
     
     
         29 . (canceled) 
     
     
         30 . (canceled) 
     
     
         31 . (canceled) 
     
     
         32 . The method of  claim 28 , comprising administering both a serotonin reuptake inhibitor and a serotonin receptor antagonist, and wherein the serotonin reuptake inhibitor is duloxetine and the serotonin receptor antagonist is WAY100635 and wherein duloxetine is administered at between 0.003 and 5 mg/kg and WAY100635 is administered at between 0.1 and 1 mg/kg. 
     
     
         33 . (canceled) 
     
     
         34 . The method of  claim 17 , further comprising administering an opioid drug to the patient, wherein the opioid drug is selected from the group consisting of tramadol, morphine, codeine, thebaine, diacetylmorphine (morphine diacetate; heroin), nicomorphine (morphine dinicotinate), dipropanoylmorphine (morphine dipropionate), desomorphine, acetylpropionylmorphine, dibenzoylmorphine, diacetyldihydromorphine, hydromorphone, hydrocodone, oxycodone, oxymorphone, ethylmorphine, buprenorphine, fentanyl, pethidine, levorphanol, methadone, dextropropoxyphene, tapentadol, endorphins, enkephalins, dynorphins, and endomorphins. 
     
     
         35 .- 43 . (canceled)