421:
with his implants in the bovine septal region and the ability of electrical stimulation to blunt or alter behavior. Further attempts at this "behavioral modification" in humans were difficult and seldom reliable, and contributed to the overall lack of progress in central nervous system neuromodulation from that era. Attempts at intractable pain syndromes were met with more success, but again hampered by the quality of technology. In particular, the so-called DBS "zero" electrode, (consisting of a contact loop on its end) had an unacceptable failure rate and revisions were fraught with more risk than benefit. Overall, attempts at using electrical stimulation for "behavioral modification" were difficult and seldom reliable, slowing development of DBS. Attempts at addressing intractable pain syndromes with DBS were met with more success, but again hampered by the quality of technology. A number of physicians who hoped to address hitherto intractable problems sought development of more specialized equipment; for instance, in the 1960s, Wall's colleague Bill Sweet recruited engineer Roger Avery to make an implantable peripheral nerve stimulator. Avery started the Avery
Company, which made a number of implantable stimulators. Shortly before his retirement in 1983, he submitted data requested by the FDA, which had begun to regulate medical devices following a 1977 meeting on the topic, regarding DBS for chronic pain. Medtronic and Neuromed also made deep brain stimulators at the time, but reportedly felt a complex safety and efficacy clinical trial in patients who were difficult to evaluate would be too costly for the size of the potential patient base, so did not submit clinical data on DBS for chronic pain to the FDA, and that indication was de-approved.
140:
a desynchronizing pulse to the cortical area that is undergoing an epileptic seizure. This concept of feed-forward stimulation will likely become more prevalent as physiological markers of targeted diseases and neural disorders are discovered and verified. The on-demand stimulation may contribute to longer battery life, if sensing and signal-processing demands of the system are sufficiently power-efficient. New electrode designs could yield more efficient and precise stimulation, requiring less current and minimizing unwanted side-stimulation. In addition, to overcome the challenge of preventing lead migration in areas of the body that are subject to motion such as turning and bending, researchers are exploring developing small stimulation systems that are recharged wirelessly rather than through an electrical lead.
417:
oversimplified, the theory held that pain transmissions from small nerve fibers can be overridden, or the gate "closed", by competing transmissions along the wider touch nerve fibers. Building on that concept, in 1967, the first dorsal column stimulator for pain control was demonstrated by Dr. Norm Shealy at
Western Reserve Medical School, using a design adapted by Tom Mortimer, a graduate student at Case Institute of Technology, from cardiac nerve stimulators by Medtronic, Inc., where he had a professional acquaintance who shared the circuit diagram. In 1973, Hosbuchi reported alleviating the denervation facial pain of anesthesia dolorosa through ongoing electrical stimulation of the somatosensory thalamus, marking the start of the age of deep brain stimulation.
373:
still intriguing questions for contemporary research. Non-invasive electrical and magnetic brain tissue stimulation targets a large area of poorly characterized tissue. Therefore, it is unclear whether electrical and magnetic fields reach only the neuronal networks of the brain that need treatment. Again, these methods involve excessive exposure to intense electrical and magnetic fields several times and even orders of magnitude higher than natural ones in the brain. However, non-invasive electrical and magnetic brain tissue methods cannot target only the neuronal networks that need to be treated. The undefined radiation target can destroy healthy cells during therapy.
220:
intractable rage, dementia, and morbid obesity. It has also shown promise for
Tourette syndrome, torticollis, and tardive dyskinesia. DBS therapy, unlike spinal cord stimulation, has a variety of central nervous system targets, depending on the target pathology. For Parkinson's disease central nervous system targets include the subthalamic nucleus, globus pallidus interna, and the ventral intermidus nucleus of the thalamus. Dystonias are often treated by implants targeting globus pallidus interna, or less often, parts of the ventral thalamic group. The anterior thalamus is the target for epilepsy.
136:"paddle" or "grid" electrodes), or stereotactic implants for the central nervous system, and an implanted pulse generator (IPG). Depending on the distance from the electrode access point an extension cable may also be added into the system. The IPG can have either a non-rechargeable battery needing replacement every 2–5 years (depending on stimulation parameters) or a rechargeable battery that is replenished via an external inductive charging system.
181:
Depending on the system, the program may elicit a tingling sensation that covers most of the painful area, replacing some of the painful sensations with more of a gentle massaging sensation, although other more recent systems do not create a tingling sensation. The patient is sent home with a handheld remote controller to turn the system off or on or switch between pre-set stimulation parameters, and can follow up to adjust the parameters.
81:, that can modulate the excitability and firing patterns of neural circuits. There may also be more direct electrophysiological effects on neural membranes as the mechanism of action of electrical interaction with neural elements. The end effect is a "normalization" of a neural network function from its perturbed state. Presumed mechanisms of action for neurostimulation include depolarizing blockade, stochastic normalization of
442:
would not involve electrical leads stimulating large nerves or spinal cords or brain centers. It might involve methods that are emerging within the neuromodulation family of therapies, such as optogenetics or some new nanotechnology. Disease states and conditions that have been discussed as targets for future electroceutical therapy include diabetes, infertility, obesity, rheumatoid arthritis, and autoimmune disorders.
173:
dorsal root ganglion in humans. All forms of spinal cord stimulation have been shown to have varying degrees of efficacy to address a variety of pharmacoresistant neuropathic or mixed (neuropathic and noiciceptive) pain syndromes such as post-laminectomy syndrome, low back pain, complex regional pain syndrome, peripheral neuropathy, peripheral vascular disease and angina.
1057:
Deer TR, Krames E, Mekhail N, Pope J, Leong M, Stanton-Hicks M, et al. (August 2014). "The appropriate use of neurostimulation: new and evolving neurostimulation therapies and applicable treatment for chronic pain and selected disease states. Neuromodulation
Appropriateness Consensus Committee".
139:
Although most systems operate via delivery of a constant train of stimulation, there is now the advent of so-called "feed-forward" stimulation where the device's activation is contingent on a physiological event, such as an epileptic seizure. In this circumstance, the device is activated and delivers
131:
Electrical stimulation using implantable devices came into modern usage in the 1980s and its techniques and applications have continued to develop and expand. These are methods where an operation is required to position an electrode. The stimulator, with the battery, similar to a pacemaker, may also
420:
Despite the limited clinical experience in these decades, that era is remarkable for the demonstration of the role technology has in neuromodulation, and there are some case reports of deep brain stimulation for a variety of problems; real or perceived. Delgado hinted at the power of neuromodulation
428:
In parallel to the development of neuromodulation systems to address motor impairment, cochlear implants were the first neuromodulation system to reach a broad commercial stage to address a functional deficit; they provide sound perception in users who are hearing-impaired due to missing or damaged
372:
Another significant challenge of non-invasive electrical and magnetic methods is to localize the effect of stimulation on specific neuronal networks that need to be treated. We still need to gain knowledge about mental processes at the cellular level. Neuronal correlates of cognitive functions are
172:
Stimulation is typically in the 20–200 Hz range, though a novel class of stimulation parameters are now emerging that employ a 10 kHz stimulation train as well as 500 Hz "burst stimulation". Kilohertz stimulation trains have been applied to both the spinal cord proper as well as the
416:
for historical review) were limited by the technology available. Heath, in the 1950s, stimulated subcortical areas and made detailed observations of behavioral changes. A new understanding of pain perception was ushered in in 1965, with the Gate Theory of Wall and
Melzack. Although now considered
368:
The first issue is the uncertain dose for healthy stimulation. While neurophysiology lacks knowledge about the nature of such a treatment of nervous diseases at the cellular level, non-invasive electrical and magnetic therapies involve excessive exposure of the brain to an intense field, which is
441:
Ultimately, the electroceuticals quest aims to find the electro-neural signature of disease and at a cellular level, in real time, play back the more normal electro-signature to help maintain the neural signature in the normal state. Unlike preceding neuromodulation therapy methods, the approach
437:
In 2012, the global pharmaceutical company GlaxoSmithKline announced an initiative in bioelectric medicine in which the autonomic nervous system's impact on the immune system and inflammatory disease might be treated through electrical stimulation rather than pharmaceutical agents. The company's
223:
DBS research targets include, but are not limited to the following areas: Cg25 for depression, the anterior limb of the internal capsule for depression as well as obsessive compulsive disorder (OCD), centromedian/parafasicularis, centromedian thalamic nuclei and the subthalamic nucleus for OCD,
180:
Patient selection is key, and candidates should pass rigorous psychological screening as well as a medical workup to assure that their pain syndrome is truly medication-resistant. After recuperating from the implant procedure, the patient will return to have the system turned on and programmed.
176:
The general process for spinal cord stimulation involves a temporary trailing of appropriate patients with an external pulse generator attached to epidural electrodes located in the lower thoracic spinal cord. The electrodes are placed either via a minimally invasive needle technique (so-called
135:
In general, neuromodulation systems deliver electrical currents and typically consist of the following components: An epidural, subdural or parenchymal electrode placed via minimally invasive needle techniques (so-called percutaneous leads) or an open surgical exposure to the target (surgical
2577:
Kumar K, Taylor RS, Jacques L, Eldabe S, Meglio M, Molet J, et al. (October 2008). "The effects of spinal cord stimulation in neuropathic pain are sustained: a 24-month follow-up of the prospective randomized controlled multicenter trial of the effectiveness of spinal cord stimulation".
1166:
Deer TR, Mekhail N, Provenzano D, Pope J, Krames E, Leong M, et al. (August 2014). "The appropriate use of neurostimulation of the spinal cord and peripheral nervous system for the treatment of chronic pain and ischemic diseases: the
Neuromodulation Appropriateness Consensus Committee".
219:
from the FDA in 2003 for motor symptoms of dystonia. It was approved in 2010 in Europe for the treatment of certain types of severe epilepsy. DBS also has shown promise, although still in research, for medically intractable psychiatric syndromes of depression, obsessive compulsive disorders,
424:
However, near this time in France and elsewhere, DBS was investigated as a substitute for lesioning of brain nuclei to control motor symptoms of movement disorders such as
Parkinson's disease, and by the mid-1990s, this reversible, non-destructive stimulation therapy had become the primary
429:
sensory cells (cilia) in the inner ear. The approach to electrical stimulation used in cochlear implants was soon modified by one manufacturer, Boston
Scientific Corporation, for design of electrical leads to be used in spinal cord stimulation treatment of chronic pain conditions.
345:), a low complexity and anatomical specificity is reached through a highly focal magnetic field. In tPEMF the stimulation has a low amplitude (0.01–500 millitesla), a high complexity and anatomical specificity is reached through the specific frequency content of the signal.
169:, an implantable pulse generator about the size of a stopwatch is placed under the skin on the trunk. It delivers mild impulses along slender electrical leads leading to small electrical contacts, about the size of a grain of rice, at the area of the spine to be stimulated.
1543:
Siebner HR, Hartwigsen G, Kassuba T, Rothwell JC (2009). "How does transcranial magnetic stimulation modify neuronal activity in the brain? Implications for studies of cognition". Cortex; A Journal
Devoted to the Study of the Nervous System and Behavior. 45 (9): 1035–1042.
2116:
Deer TR, Prager J, Levy R, Rathmell J, Buchser E, Burton A, et al. (2012). "Polyanalgesic
Consensus Conference 2012: recommendations for the management of pain by intrathecal (intraspinal) drug delivery: report of an interdisciplinary expert panel".
108:). Technical improvements include a trend toward minimally invasive (or noninvasive) systems; as well as smaller, more sophisticated devices that may have automated feedback control, and conditional compatibility with magnetic resonance imaging.
89:, reduction of neural firing keratosis, and suppression of neural network oscillations. Although the exact mechanisms of neurostimulation are not known, the empirical effectiveness has led to considerable application clinically.
49:
is "the alteration of nerve activity through targeted delivery of a stimulus, such as electrical stimulation or chemical agents, to specific neurological sites in the body". It is carried out to normalize – or modulate –
1556:
Sparing R, Mottaghy FM (2008). "Noninvasive brain stimulation with transcranial magnetic or direct current stimulation (TMS/tDCS)-From insights into human memory to therapy of its dysfunction". Methods. 44 (4): 329–337.
1516:
Benussi A, Pascual-Leone A, Borroni B (2020). "Non-Invasive Cerebellar Stimulation in Neurodegenerative Ataxia: A Literature Review". International Journal of Molecular Sciences. 21 (6): 1948. doi:10.3390/ijms21061948
1534:
Grimaldi G, Argyropoulos GP, Boehringer A, Celnik P, Edwards MJ, Ferrucci R, et al. (2014). "Non-invasive cerebellar stimulation--a consensus paper" (PDF). Cerebellum. 13 (1): 121–138. doi:10.1007/s12311-013-0514-7
2427:
69:
Neuromodulation, whether electrical or magnetic, employs the body's natural biological response by stimulating nerve cell activity that can influence populations of nerves by releasing transmitters, such as
412:
Electrical stimulation of the nervous system has a long and complex history. Earlier practitioners of deep brain stimulation in the latter half of the 20th century (Delgado, Heath, Hosbuchi. See Hariz
2797:
Operative Neuromodulation Acta Neurochirurgica Supplements: An introduction to operative neuromodulation and functional neuroprosthetics, the new frontiers of clinical neuroscience and biotechnology
1958:
Althaus J: A Treatise on Medical Electricity, Theoretical and Practical; and Its Use in the Treatment of Paralysis, Neuralgia, and Other Diseases Philadelphia, Lindsay & Blakiston, 1860;163-170.
1314:"Medtronic Receives European CE Mark Approval for Deep Brain Stimulation Therapy for Refractory Epilepsy Further Clinical Study Required for Application to U.S. Food and Drug Administration"
438:
first investment in 2013 involved a small startup company, SetPoint Medical, which was developing neurostimulators to address inflammatory autoimmune disorders such as rheumatoid arthritis.
891:
Matsumura Y, Hirayama T, Yamamoto T (2013). "Comparison between pharmacologic evaluation and repetitive transcranial magnetic stimulation-induced analgesia in poststroke pain patients".
66:), and by 2014, these had been at minimum demonstrated in mammalian models, or first-in-human data had been acquired. The most clinical experience has been with electrical stimulation.
1408:
George MS, Nahas Z, Borckardt JJ, Anderson B, Burns C, Kose S, Short EB (January 2007). "Vagus nerve stimulation for the treatment of depression and other neuropsychiatric disorders".
1313:
2540:
Krames ES, Monis S, Poree L, Deer T, Levy R (2011). "Using the SAFE principles when evaluating electrical stimulation therapies for the pain of failed back surgery syndrome".
1467:"Emerging synergisms between drugs and physiologically-patterned weak magnetic fields: implications for neuropharmacology and the human population in the twenty-first century"
62:, or a drug instilled directly in the subdural space (intrathecal drug delivery). Emerging applications involve targeted introduction of genes or gene regulators and light (
2219:
Francisco GE, Hu MM, Boake C, Ivanhoe CB (May 2005). "Efficacy of early use of intrathecal baclofen therapy for treating spastic hypertonia due to acquired brain injury".
425:
application of DBS in appropriate patients, to slow progression of movement impairment from the disease and reduce side effects from long-term, escalating medication use.
272:
Peripheral nerve stimulation (PNS, which refers to simulation of nerves beyond the spine or brain, and may be considered to include occipital or sacral nerve stimulation)
3174:
2685:
Petropoulou KB, Panourias IG, Rapidi CA, Sakas DE (2006). "The phenomenon of spasticity: A pathophysiological and clinical introduction to neuromodulation therapies".
2431:
727:
1569:
Kirsch, D. L., & Nichols, F. (2013). Cranial electrotherapy stimulation for treatment of anxiety, depression, and insomnia. Psychiatric Clinics, 36(1), 169-176.
96:, chronic head pain conditions, and functional therapy ranging from bladder and bowel or respiratory control to improvement of sensory deficits, such as hearing (
2198:
Dormandy JA, Rutherford RB (January 2000). "Management of peripheral arterial disease (PAD). TASC Working Group. TransAtlantic Inter-Society Consensus (TASC)".
1717:
Benabid AL, Chabardes S, Torres N, Piallat B, Krack P, Fraix V, Pollak P (2009). "Functional neurosurgery for movement disorders: a historical perspective".
384:
Chemical neuromodulation is always invasive, because a drug is delivered in a highly specific location of the body. The non-invasive variant is traditional
86:
1843:
165:. In patients who experience pain reduction of 50 percent or more during a temporary trial, a permanent implant may be offered in which, as with a
157:
is a form of invasive neuromodulation therapy in common use since the 1980s. Its principal use is as a reversible, non-pharmacological therapy for
848:
Shupak NM, Prato FS, Thomas AW (June 2004). "Human exposure to a specific pulsed magnetic field: effects on thermal sensory and pain thresholds".
376:
Additionally, these methods are not generalizable to all patients because of more inter-individual variability in response to brain stimulation.
1674:
Bittar RG, Kar-Purkayastha I, Owen SL, Bear RE, Green A, Wang S, Aziz TZ (June 2005). "Deep brain stimulation for pain relief: a meta-analysis".
2355:
Gracies JM, Nance P, Elovic E, McGuire J, Simpson DM (1997). "Traditional pharmacological treatments for spacticity part I: local treatments".
322:
Magnetic methods of neuromodulation are normally non-invasive: no surgery is required to allow a magnetic field to enter the body because the
2812:
Sharan AD, Rezai AR. Neurostimulation for Epilepsy. In: Krames ES, Peckham HP, Rezai AR, eds. Neuromodulation. London: Elsevier; 2009:617–66.
1317:
791:"A novel magnetic stimulator increases experimental pain tolerance in healthy volunteers - a double-blind sham-controlled crossover study"
2861:"Spinal cord stimulation and pain relief in painful diabetic peripheral neuropathy: a prospective two-center randomized controlled trial"
1525:
Rosa, MA; Lisanby, SH (2012). "Somatic treatments for mood disorders". Neuropsychopharmacology. 37 (1): 102–116. doi:10.1038/npp.2011.225
305:
301:
1101:
Mekhail NA, Cheng J, Narouze S, Kapural L, Mekhail MN, Deer T (2010). "Clinical applications of neurostimulation: forty years later".
2079:
Beric A, Kelly PJ, Rezai A, Sterio D, Mogilner A, Zonenshayn M, Kopell B (2001). "Complications of deep brain stimulation surgery".
3199:
341:
currents in the body. There are however differences in approach and hardware. In rTMS the stimulation has a high amplitude (0.5–3
2386:"Deep brain stimulation of the ventral internal capsule/ventral striatum for obsessive-compulsive disorder: worldwide experience"
296:
2368:
2894:
Stanton-Hicks M, Salamon J (January 1997). "Stimulation of the central and peripheral nervous system for the control of pain".
476:
289:
These methods use external electrodes to apply a current to the body in order to change the functioning of the nervous system.
54:
function. Neuromodulation is an evolving therapy that can involve a range of electromagnetic stimuli such as a magnetic field (
365:
Brain tissue stimulation using non-invasive electrical and magnetic methods raises several concerns, including the following:
2841:
2757:
2702:
466:
266:
354:
224:
anorexia and Tourette syndrome, the nucleus accumbens and ventral striatum have also been assayed for depression and pain.
731:
1145:
3125:
Zafonte R, Lombard L, Elovic E (October 2004). "Antispasticity medications: uses and limitations of enteral therapy".
2740:
Ratto C, Parello A, Donisi L, Doglietto GB (2006). "Sacral neuromodulation in the treatment of defecation disorders".
2484:
Kellaway P (July 1946). "The part played by electric fish in the early history of bioelectricity and electrotherapy".
662:
Wu C, Sharan AD (2013). "Neurostimulation for the treatment of epilepsy: a review of current surgical interventions".
1734:
1637:
995:
728:"Medtronic Introduces the First and Only Neurostimulation Systems for Chronic Pain Designed for Full-Body MRI Safety"
649:
349:
250:
55:
1580:
3204:
323:
937:
Feng WW, Bowden MG, Kautz S (2013). "Review of transcranial direct current stimulation in poststroke recovery".
2156:"Spinal cord stimulation in patients with painful diabetic neuropathy: a multicentre randomized clinical trial"
1760:"Healthcare: Into the cortex Scientific advances on the brain promise to transform the pharmaceutical industry"
471:
2650:
Mannheimer C, Eliasson T, Augustinsson LE, Blomstrand C, Emanuelsson H, Larsson S, et al. (March 1998).
216:
2968:"Spinal cord stimulation for critical leg ischemia: a review of effectiveness and optimal patient selection"
2155:
3189:
2256:
Francisco GE, Saulino MF, Yablon SA, Turner M (September 2009). "Intrathecal baclofen therapy: an update".
1922:
Aló KM, Holsheimer J (April 2002). "New trends in neuromodulation for the management of neuropathic pain".
1451:
776:
for "Functional Neuromodulation Ltd. ADvance DBS-f in Patients With Mild Probable Alzheimer's Disease." at
212:
705:
2652:"Electrical stimulation versus coronary artery bypass surgery in severe angina pectoris: the ESBY study"
1759:
233:
101:
1210:
Bronstein JM, Tagliati M, Alterman RL, Lozano AM, Volkmann J, Stefani A, et al. (February 2011).
2859:
Slangen R, Schaper NC, Faber CG, Joosten EA, Dirksen CD, van Dongen RT, et al. (November 2014).
481:
334:
326:
of tissue is similar to that of air. In other words: magnetic fields penetrate the body very easily.
311:
116:
2787:
2732:
2447:
Jobst BC (September 2010). "Electrical stimulation in epilepsy: vagus nerve and brain stimulation".
369:
several times and even orders of magnitude higher than natural electromagnetic fields in the brain.
3219:
3214:
3209:
789:
Kortekaas R, van Nierop LE, Baas VG, Konopka KH, Harbers M, van der Hoeven JH, et al. (2013).
456:
278:
92:
Existing and emerging neuromodulation treatments also include application in medication-resistant
3169:
2154:
de Vos CC, Meier K, Zaalberg PB, Nijhuis HJ, Duyvendak W, Vesper J, et al. (November 2014).
1868:
Birmingham K, Gradinaru V, Anikeeva P, Grill WM, Pikov V, McLaughlin B, et al. (June 2014).
261:
255:
154:
149:
2384:
Greenberg BD, Gabriels LA, Malone DA, Rezai AR, Friehs GM, Okun MS, et al. (January 2010).
2042:
Ben-Menachem E (September 2001). "Vagus nerve stimulation, side effects, and long-term safety".
200:
196:
190:
112:
2817:
1999:
Attal N, Cruccu G, Haanpää M, Hansson P, Jensen TS, Nurmikko T, et al. (November 2006).
1869:
2615:
Mallet L, Polosan M, Jaafari N, Baup N, Welter ML, Fontaine D, et al. (November 2008).
1212:"Deep brain stimulation for Parkinson disease: an expert consensus and review of key issues"
706:"Precision™ Plus Spinal Cord Stimulator System Receives CE Mark Approval as MRI Conditional"
1798:
802:
8:
1802:
806:
395:
drug delivery systems (ITDS, which may deliver micro-doses of painkiller (for instance,
3150:
3138:
3073:
3046:
3027:
3002:
2949:
2924:
2775:
2720:
2603:
2591:
2565:
2507:"Spinal cord stimulation for chronic reflex sympathetic dystrophy--five-year follow-up"
2472:
2410:
2385:
2372:
2281:
2244:
2186:
2142:
2104:
2067:
2030:
1987:
1947:
1900:
1819:
1786:
1699:
1610:
1491:
1466:
1433:
1290:
1265:
1236:
1211:
1192:
1126:
1083:
1034:
1009:
987:
962:
916:
873:
825:
790:
777:
759:
687:
641:
623:
580:
451:
2984:
2967:
1726:
3142:
3113:
3078:
3032:
2989:
2954:
2911:
2907:
2882:
2847:
2837:
2763:
2753:
2708:
2698:
2673:
2638:
2607:
2595:
2557:
2553:
2528:
2493:
2464:
2415:
2346:
2329:
2316:
2273:
2236:
2207:
2178:
2134:
2130:
2096:
2059:
2055:
2022:
2017:
2000:
1991:
1979:
1975:
1939:
1935:
1892:
1824:
1740:
1730:
1691:
1633:
1602:
1496:
1425:
1390:
1295:
1241:
1184:
1118:
1114:
1075:
1039:
991:
990:; Rezai, Ali R., eds. (2009). Neuromodulation, Vol. 1-2. Academic Press. pp. 1–1200.
954:
920:
908:
865:
830:
679:
675:
645:
615:
572:
509:
166:
97:
2569:
2476:
2285:
2248:
2190:
2146:
2108:
2034:
1904:
1703:
1614:
1437:
1196:
1130:
1087:
966:
877:
627:
584:
111:
Neuromodulation therapy has been investigated for other chronic conditions, such as
3154:
3134:
3103:
3068:
3058:
3022:
3018:
3014:
2979:
2944:
2936:
2903:
2872:
2829:
2745:
2690:
2663:
2628:
2587:
2549:
2518:
2505:
Kemler MA, de Vet HC, Barendse GA, van den Wildenberg FA, van Kleef M (June 2006).
2456:
2405:
2397:
2376:
2364:
2341:
2306:
2265:
2228:
2170:
2126:
2088:
2071:
2051:
2012:
1971:
1951:
1931:
1884:
1814:
1806:
1722:
1683:
1592:
1486:
1478:
1417:
1380:
1285:
1277:
1231:
1223:
1176:
1110:
1067:
1029:
1021:
946:
900:
857:
820:
810:
691:
671:
607:
562:
499:
489:
237:
208:
59:
772:
754:
2749:
2694:
1385:
1368:
861:
815:
644:; Rezai, Ali R., eds. (2009). Neuromodulation, Vol. 1-2. Academic Press. p. 274.
611:
598:
Al-Otaibi FA, Hamani C, Lozano AM (October 2011). "Neuromodulation in epilepsy".
494:
385:
177:
percutaneous leads) or an open surgical exposure (surgical "paddle" electrodes).
105:
20:
3003:"Spinal cord stimulation for non-reconstructable chronic critical leg ischaemia"
1844:"GlaxoSmithKline stakes a pioneering effort to launch 'electroceutical' R&D"
1227:
2940:
2269:
2174:
1687:
1482:
1025:
245:
51:
2668:
2651:
2460:
2311:
2294:
2232:
1597:
567:
550:
360:
215:
in 1997 for essential tremor, in 2002 for Parkinson's disease, and received a
3194:
3183:
3063:
1339:
330:
82:
1962:
Andrews RJ (June 2010). "Neuromodulation: advances in the next five years".
1421:
1369:"Probing and regulating dysfunctional circuits using deep brain stimulation"
3146:
3117:
3092:"How to clinically assess and treat muscle overactivity in spastic paresis"
3082:
3036:
2993:
2958:
2886:
2851:
2767:
2712:
2642:
2599:
2561:
2532:
2497:
2468:
2419:
2320:
2277:
2240:
2211:
2182:
2138:
2100:
2063:
2026:
1983:
1943:
1896:
1828:
1744:
1695:
1606:
1500:
1429:
1394:
1299:
1266:"Deep brain stimulation (DBS) at the interface of neurology and psychiatry"
1245:
1188:
1122:
1079:
1043:
958:
912:
869:
834:
683:
619:
576:
504:
342:
158:
63:
3108:
3091:
2915:
2677:
2633:
2616:
758:
for "Deep Brain Stimulation for the Treatment of Alzheimer's Disease." at
36:
2617:"Subthalamic nucleus stimulation in severe obsessive-compulsive disorder"
392:
162:
78:
2649:
2523:
2506:
2295:"Cochlear implantation in adults: a systematic review and meta-analysis"
2401:
2293:
Gaylor JM, Raman G, Chung M, Lee J, Rao M, Lau J, Poe DS (March 2013).
950:
396:
329:
The two main techniques are highly related in that both use changes in
2877:
2860:
2833:
2504:
2092:
1180:
1071:
904:
549:
Karas PJ, Mikell CB, Christian E, Liker MA, Sheth SA (November 2013).
19:
This article is about the therapy. For the physiological process, see
1452:"Premarket Approval (PMA) Inspire II Upper Airway Stimulation System"
1281:
461:
195:
Another invasive neuromodulation treatment developed in the 1980s is
2689:. Acta Neurochirurgica Supplements. Vol. 97. pp. 137–144.
1888:
1810:
260:
Hypoglossal nerve stimulation, an option for some patients who have
2744:. Acta Neurochirurgica Supplements. Vol. 97. pp. 341–50.
2369:
10.1002/(SICI)1097-4598(1997)6+<61::AID-MUS6>3.0.CO;2-H
400:
204:
199:, which may be used to help limit symptoms of movement disorder in
93:
71:
3175:
Neuromodulation Appropriateness Consensus Committee (news release)
2001:"EFNS guidelines on pharmacological treatment of neuropathic pain"
528:
730:. Minneapolis, MN: Medtronic, Inc. August 6, 2013. Archived from
241:
75:
1867:
1719:
Neurotherapy: Progress in Restorative Neuroscience and Neurology
1581:"Deep brain stimulation between 1947 and 1987: the untold story"
119:, chronic pain, and as an adjunctive treatment in recovery from
2925:"Responsive cortical stimulation for the treatment of epilepsy"
2684:
1209:
1010:"Responsive cortical stimulation for the treatment of epilepsy"
708:. Paris, France: Boston Scientific Corporation. August 28, 2012
236:, which provides a sense of sound to a person who cannot use a
120:
2428:"Recently-Approved Devices - VNS Therapy System - P970003s050"
1721:. Progress in Brain Research. Vol. 175. pp. 379–91.
788:
126:
1785:
Famm K, Litt B, Tracey KJ, Boyden ES, Slaoui M (April 2013).
1716:
1673:
1340:"Thalamic Stimulation: New Approach to Treatment of Epilepsy"
279:
Sacral nerve stimulation (SNS) / sacral neuromodulation (SNM)
2383:
2255:
1552:
1550:
1407:
3090:
Yelnik AP, Simon O, Parratte B, Gracies JM (October 2010).
2739:
1259:
1257:
1255:
551:"Deep brain stimulation: a mechanistic and clinical update"
361:
Limitations of non-invasive electrical and magnetic methods
3127:
American Journal of Physical Medicine & Rehabilitation
3089:
2858:
2153:
1565:
1563:
1100:
2354:
1998:
1632:(2nd ed.). New York: Penguin Books. pp. 61–69.
1547:
1165:
890:
548:
338:
2614:
2576:
2330:"History of electrical neuromodulation for chronic pain"
1252:
2218:
1669:
1667:
1651:
1649:
1560:
161:
management that delivers mild electrical pulses to the
2808:(2nd ed.). London, United Kingdom: Martin Dunitz.
2115:
1655:
308:, transcutaneous afferent patterned stimulation (TAPS)
3044:
2078:
1621:
1362:
1360:
1056:
597:
3124:
2893:
2539:
1784:
1664:
1658:
Textbook of Stereotactic and Functional Neurosurgery
1646:
1578:
1454:. U.S. Food and Drug Administration. April 30, 2014.
227:
3170:
Neuromodulation: Technology at the Neural Interface
2430:. U.S. Food and Drug Administration. Archived from
2292:
1787:"Drug discovery: a jump-start for electroceuticals"
432:
350:
Repetitive transcranial magnetic stimulation (rTMS)
2794:
2197:
1656:Lozano AM, Gildenberg PL, Tasker RR, eds. (2009).
1357:
1316:(Press release). 16 September 2010. Archived from
355:Transcranial pulsed electromagnetic fields (tPEMF)
302:Transcutaneous electrical nerve stimulation (TENS)
284:
211:. Deep brain stimulation was approved by the U.S.
1464:
847:
529:"International Neuromodulation Society home page"
3181:
2922:
2804:Schachter SC, Schmidt D (2003). "Introduction".
2803:
1007:
317:
3000:
2965:
1579:Hariz MI, Blomstedt P, Zrinzo L (August 2010).
1512:
1510:
936:
2923:Sun FT, Morrell MJ, Wharen RE (January 2008).
2795:Sakas DE, Simpson BA, Krames ES, eds. (2007).
1203:
1008:Sun FT, Morrell MJ, Wharen RE (January 2008).
884:
297:Transcranial direct current stimulation (tDCS)
132:be implanted, or may remain outside the body.
1921:
1870:"Bioelectronic medicines: a research roadmap"
1366:
591:
2041:
1507:
1263:
1001:
932:
930:
841:
782:
379:
267:Percutaneous tibial nerve stimulation (PTNS)
3007:The Cochrane Database of Systematic Reviews
2299:JAMA Otolaryngology–Head & Neck Surgery
1627:
1465:Whissell PD, Persinger MA (December 2007).
1401:
127:Invasive electrical neuromodulation methods
74:, or other chemical messengers such as the
2327:
1964:Annals of the New York Academy of Sciences
143:
3107:
3072:
3062:
3026:
2983:
2948:
2876:
2818:"History of peripheral nerve stimulation"
2667:
2632:
2522:
2409:
2345:
2310:
2016:
1818:
1596:
1490:
1384:
1289:
1235:
1033:
982:
980:
978:
976:
927:
824:
814:
566:
184:
3045:Yampolsky C, Hem S, Bendersky D (2012).
3001:Ubbink DT, Vermeulen H (February 2013).
2483:
2081:Stereotactic and Functional Neurosurgery
661:
3047:"Dorsal column stimulator applications"
1961:
1841:
1757:
1161:
1159:
251:Functional electrical stimulation (FES)
3182:
2972:Journal of Pain and Symptom Management
2815:
2449:Current Treatment Options in Neurology
1883:(6) (published 30 May 2014): 399–400.
1367:Lozano AM, Lipsman N (February 2013).
1337:
1264:Williams NR, Okun MS (November 2013).
1143:
973:
477:North American Neuromodulation Society
2966:Ubbink DT, Vermeulen H (April 2006).
2446:
1572:
1270:The Journal of Clinical Investigation
1146:"A remote control turns off my spine"
467:International Neuromodulation Society
1156:
2896:Journal of Clinical Neurophysiology
2621:The New England Journal of Medicine
2511:The New England Journal of Medicine
2486:Bulletin of the History of Medicine
2044:Journal of Clinical Neurophysiology
13:
3139:10.1097/01.phm.0000141132.48673.fa
3096:Journal of Rehabilitation Medicine
2592:10.1227/01.NEU.0000325731.46702.D9
1914:
1410:Expert Review of Neurotherapeutics
1144:Bailey, Madeleine (May 14, 2013).
521:
399:) or anti-spasm medicine (such as
269:for the treatment of incontinence.
14:
3231:
3163:
2985:10.1016/j.jpainsymman.2005.12.013
403:) directly to the site of action)
275:Occipital nerve stimulation (ONS)
228:Other invasive electrical methods
3051:Surgical Neurology International
2908:10.1097/00004691-199701000-00004
2822:Progress in Neurological Surgery
2799:. Vienna: Springer. p. 482.
2554:10.1111/j.1525-1403.2011.00373.x
2347:10.1111/j.1526-4637.2006.00118.x
2131:10.1111/j.1525-1403.2012.00476.x
2056:10.1097/00004691-200109000-00005
2018:10.1111/j.1468-1331.2006.01511.x
1976:10.1111/j.1749-6632.2009.05379.x
1936:10.1097/00006123-200204000-00003
1930:(4): 690–703, discussion 703–4.
1676:Journal of Clinical Neuroscience
1544:doi:10.1016/j.cortex.2009.02.007
1115:10.1111/j.1533-2500.2009.00341.x
676:10.1111/j.1525-1403.2012.00501.x
457:Brain computer interfacing (BCI)
433:Relationship to electroceuticals
3200:Physical psychiatric treatments
2125:(5): 436–64, discussion 464–6.
1861:
1835:
1778:
1751:
1710:
1557:doi:10.1016/j.ymeth.2007.02.001
1537:
1528:
1519:
1458:
1444:
1331:
1306:
1137:
1094:
1050:
939:Topics in Stroke Rehabilitation
312:Electroconvulsive therapy (ECT)
285:Non-invasive electrical methods
3019:10.1002/14651858.CD004001.pub3
2548:(4): 299–311, discussion 311.
1877:Nature Reviews. Drug Discovery
1660:. Vol. 1. pp. 16–20.
1066:(6): 599–615, discussion 615.
764:
746:
720:
698:
655:
634:
542:
472:Interventional pain management
304:and a prescription variant of
1:
2586:(4): 762–70, discussion 770.
2005:European Journal of Neurology
1727:10.1016/S0079-6123(09)17525-8
1175:(6): 515–50, discussion 550.
899:(4): 349–54, discussion 354.
606:(4): 957–79, discussion 979.
515:
318:Non-invasive magnetic methods
256:Vagus nerve stimulation (VNS)
217:humanitarian device exemption
2750:10.1007/978-3-211-33079-1_45
2695:10.1007/978-3-211-33079-1_19
1386:10.1016/j.neuron.2013.01.020
862:10.1016/j.neulet.2004.03.069
816:10.1371/journal.pone.0061926
612:10.1227/NEU.0b013e31822b30cd
388:, e.g. swallowing a tablet.
240:due to a damaged or missing
213:Food and Drug Administration
7:
2200:Journal of Vascular Surgery
1842:Carroll J (10 April 2013).
1628:Wall PD, Melzack R (1996).
1228:10.1001/archneurol.2010.260
670:(1): 10–24, discussion 24.
445:
102:auditory brainstem implants
10:
3236:
2941:10.1016/j.nurt.2007.10.069
2270:10.1016/j.pmrj.2009.07.015
2175:10.1016/j.pain.2014.08.031
1758:Cookson C (31 July 2012).
1688:10.1016/j.jocn.2004.10.005
1483:10.2174/157015907782793603
1338:Wilner A (22 April 2010).
1026:10.1016/j.nurt.2007.10.069
407:
234:Auditory brainstem implant
188:
147:
18:
2742:Operative Neuromodulation
2687:Operative Neuromodulation
2669:10.1161/01.cir.97.12.1157
2461:10.1007/s11940-010-0087-4
2312:10.1001/jamaoto.2013.1744
2233:10.1080/02699050400003999
1598:10.3171/2010.4.FOCUS10106
1471:Current Neuropharmacology
568:10.3171/2013.9.focus13383
380:Invasive chemical methods
33:
28:
3064:10.4103/2152-7806.103019
2806:Vagus Nerve Stimulation
1422:10.1586/14737175.7.1.63
331:magnetic field strength
262:obstructive sleep apnea
155:Spinal cord stimulation
150:Spinal cord stimulation
144:Spinal cord stimulation
3205:Neurological disorders
2328:Gildenberg PL (2006).
770:Clinical trial number
752:Clinical trial number
197:deep brain stimulation
191:Deep brain stimulation
185:Deep brain stimulation
3109:10.2340/16501977-0613
2634:10.1056/nejmoa0708514
1630:The challenge of pain
1216:Archives of Neurology
324:magnetic permeability
3057:(Suppl 4): S275-89.
2390:Molecular Psychiatry
850:Neuroscience Letters
337:electric fields and
3190:Implants (medicine)
3133:(10 Suppl): S50-8.
2524:10.1056/nejmc055504
2206:(1 Pt 2): S1–S296.
1803:2013Natur.496..159F
1585:Neurosurgical Focus
986:Krames, Elliot S.;
807:2013PLoSO...861926K
640:Krames, Elliot S.;
555:Neurosurgical Focus
201:Parkinson's disease
113:Alzheimer's disease
2978:(4 Suppl): S30-5.
2816:Slavin KV (2011).
2402:10.1038/mp.2008.55
1344:Medscape Neurology
988:Peckham, P. Hunter
951:10.1310/tsr2001-68
778:ClinicalTrials.gov
760:ClinicalTrials.gov
642:Peckham, P. Hunter
452:Alim-Louis Benabid
2929:Neurotherapeutics
2878:10.2337/dc14-0684
2843:978-3-8055-9489-9
2834:10.1159/000323002
2759:978-3-211-33078-4
2704:978-3-211-33078-4
2093:10.1159/000064600
1181:10.1111/ner.12208
1072:10.1111/ner.12204
1014:Neurotherapeutics
905:10.1111/ner.12019
510:Visual prosthesis
292:Methods include:
167:cardiac pacemaker
98:cochlear implants
44:
43:
3227:
3158:
3121:
3111:
3086:
3076:
3066:
3040:
3030:
2997:
2987:
2962:
2952:
2919:
2890:
2880:
2855:
2809:
2800:
2791:
2785:
2781:
2779:
2771:
2736:
2730:
2726:
2724:
2716:
2681:
2671:
2646:
2636:
2611:
2573:
2536:
2526:
2501:
2480:
2443:
2441:
2439:
2423:
2413:
2380:
2351:
2349:
2324:
2314:
2289:
2252:
2215:
2194:
2160:
2150:
2112:
2075:
2038:
2020:
1995:
1955:
1909:
1908:
1874:
1865:
1859:
1858:
1856:
1854:
1839:
1833:
1832:
1822:
1797:(7444): 159–61.
1782:
1776:
1775:
1773:
1771:
1755:
1749:
1748:
1714:
1708:
1707:
1671:
1662:
1661:
1653:
1644:
1643:
1625:
1619:
1618:
1600:
1576:
1570:
1567:
1558:
1554:
1545:
1541:
1535:
1532:
1526:
1523:
1517:
1514:
1505:
1504:
1494:
1462:
1456:
1455:
1448:
1442:
1441:
1405:
1399:
1398:
1388:
1364:
1355:
1354:
1352:
1350:
1335:
1329:
1328:
1326:
1325:
1320:on 17 April 2019
1310:
1304:
1303:
1293:
1282:10.1172/JCI68341
1261:
1250:
1249:
1239:
1207:
1201:
1200:
1163:
1154:
1153:
1141:
1135:
1134:
1098:
1092:
1091:
1054:
1048:
1047:
1037:
1005:
999:
984:
971:
970:
934:
925:
924:
888:
882:
881:
845:
839:
838:
828:
818:
786:
780:
768:
762:
750:
744:
743:
741:
739:
724:
718:
717:
715:
713:
702:
696:
695:
659:
653:
638:
632:
631:
595:
589:
588:
570:
546:
540:
539:
537:
535:
525:
500:Neurostimulation
490:Neuroprosthetics
238:cochlear implant
209:essential tremor
106:retinal implants
60:electric current
37:edit on Wikidata
26:
25:
3235:
3234:
3230:
3229:
3228:
3226:
3225:
3224:
3220:Neurotechnology
3215:Neuropsychology
3210:Neurophysiology
3180:
3179:
3166:
3161:
3013:(2): CD004001.
2871:(11): 3016–24.
2844:
2783:
2782:
2773:
2772:
2760:
2728:
2727:
2718:
2717:
2705:
2662:(12): 1157–63.
2627:(20): 2121–34.
2542:Neuromodulation
2437:
2435:
2434:on 2 March 2016
2426:
2169:(11): 2426–31.
2158:
2119:Neuromodulation
2011:(11): 1153–69.
1917:
1915:Further reading
1912:
1889:10.1038/nrd4351
1872:
1866:
1862:
1852:
1850:
1840:
1836:
1811:10.1038/496159a
1783:
1779:
1769:
1767:
1764:Financial Times
1756:
1752:
1737:
1715:
1711:
1672:
1665:
1654:
1647:
1640:
1626:
1622:
1577:
1573:
1568:
1561:
1555:
1548:
1542:
1538:
1533:
1529:
1524:
1520:
1515:
1508:
1463:
1459:
1450:
1449:
1445:
1406:
1402:
1365:
1358:
1348:
1346:
1336:
1332:
1323:
1321:
1312:
1311:
1307:
1276:(11): 4546–56.
1262:
1253:
1208:
1204:
1169:Neuromodulation
1164:
1157:
1142:
1138:
1099:
1095:
1060:Neuromodulation
1055:
1051:
1006:
1002:
985:
974:
935:
928:
893:Neuromodulation
889:
885:
846:
842:
787:
783:
769:
765:
751:
747:
737:
735:
726:
725:
721:
711:
709:
704:
703:
699:
664:Neuromodulation
660:
656:
639:
635:
596:
592:
547:
543:
533:
531:
527:
526:
522:
518:
495:Neurotechnology
483:Neuromodulation
448:
435:
410:
386:pharmacotherapy
382:
363:
320:
287:
230:
193:
187:
152:
146:
129:
87:axonal blockade
47:Neuromodulation
40:
29:Neuromodulation
24:
21:Neuromodulation
17:
16:Type of therapy
12:
11:
5:
3233:
3223:
3222:
3217:
3212:
3207:
3202:
3197:
3192:
3178:
3177:
3172:
3165:
3164:External links
3162:
3160:
3159:
3122:
3087:
3042:
2998:
2963:
2920:
2891:
2856:
2842:
2813:
2810:
2801:
2792:
2784:|journal=
2758:
2737:
2729:|journal=
2703:
2682:
2647:
2612:
2574:
2537:
2517:(22): 2394–6.
2502:
2481:
2444:
2424:
2381:
2363:(S6): S1–S92.
2352:
2325:
2290:
2253:
2216:
2195:
2151:
2113:
2076:
2039:
1996:
1959:
1956:
1918:
1916:
1913:
1911:
1910:
1860:
1848:Fierce Biotech
1834:
1777:
1750:
1735:
1709:
1663:
1645:
1638:
1620:
1571:
1559:
1546:
1536:
1527:
1518:
1506:
1457:
1443:
1400:
1356:
1330:
1305:
1251:
1202:
1155:
1136:
1093:
1049:
1000:
972:
926:
883:
840:
781:
763:
745:
719:
697:
654:
633:
590:
541:
519:
517:
514:
513:
512:
507:
502:
497:
492:
487:
479:
474:
469:
464:
459:
454:
447:
444:
434:
431:
409:
406:
405:
404:
381:
378:
362:
359:
358:
357:
352:
319:
316:
315:
314:
309:
299:
286:
283:
282:
281:
276:
273:
270:
264:
258:
253:
248:
246:auditory nerve
229:
226:
189:Main article:
186:
183:
148:Main article:
145:
142:
128:
125:
104:) and vision (
52:nervous tissue
42:
41:
34:
31:
30:
15:
9:
6:
4:
3:
2:
3232:
3221:
3218:
3216:
3213:
3211:
3208:
3206:
3203:
3201:
3198:
3196:
3193:
3191:
3188:
3187:
3185:
3176:
3173:
3171:
3168:
3167:
3156:
3152:
3148:
3144:
3140:
3136:
3132:
3128:
3123:
3119:
3115:
3110:
3105:
3101:
3097:
3093:
3088:
3084:
3080:
3075:
3070:
3065:
3060:
3056:
3052:
3048:
3043:
3038:
3034:
3029:
3024:
3020:
3016:
3012:
3008:
3004:
2999:
2995:
2991:
2986:
2981:
2977:
2973:
2969:
2964:
2960:
2956:
2951:
2946:
2942:
2938:
2934:
2930:
2926:
2921:
2917:
2913:
2909:
2905:
2901:
2897:
2892:
2888:
2884:
2879:
2874:
2870:
2866:
2865:Diabetes Care
2862:
2857:
2853:
2849:
2845:
2839:
2835:
2831:
2827:
2823:
2819:
2814:
2811:
2807:
2802:
2798:
2793:
2789:
2777:
2769:
2765:
2761:
2755:
2751:
2747:
2743:
2738:
2734:
2722:
2714:
2710:
2706:
2700:
2696:
2692:
2688:
2683:
2679:
2675:
2670:
2665:
2661:
2657:
2653:
2648:
2644:
2640:
2635:
2630:
2626:
2622:
2618:
2613:
2609:
2605:
2601:
2597:
2593:
2589:
2585:
2581:
2575:
2571:
2567:
2563:
2559:
2555:
2551:
2547:
2543:
2538:
2534:
2530:
2525:
2520:
2516:
2512:
2508:
2503:
2499:
2495:
2492:(2): 112–37.
2491:
2487:
2482:
2478:
2474:
2470:
2466:
2462:
2458:
2455:(5): 443–53.
2454:
2450:
2445:
2433:
2429:
2425:
2421:
2417:
2412:
2407:
2403:
2399:
2395:
2391:
2387:
2382:
2378:
2374:
2370:
2366:
2362:
2358:
2353:
2348:
2343:
2339:
2335:
2331:
2326:
2322:
2318:
2313:
2308:
2305:(3): 265–72.
2304:
2300:
2296:
2291:
2287:
2283:
2279:
2275:
2271:
2267:
2263:
2259:
2254:
2250:
2246:
2242:
2238:
2234:
2230:
2227:(5): 359–64.
2226:
2222:
2217:
2213:
2209:
2205:
2201:
2196:
2192:
2188:
2184:
2180:
2176:
2172:
2168:
2164:
2157:
2152:
2148:
2144:
2140:
2136:
2132:
2128:
2124:
2120:
2114:
2110:
2106:
2102:
2098:
2094:
2090:
2087:(1–4): 73–8.
2086:
2082:
2077:
2073:
2069:
2065:
2061:
2057:
2053:
2049:
2045:
2040:
2036:
2032:
2028:
2024:
2019:
2014:
2010:
2006:
2002:
1997:
1993:
1989:
1985:
1981:
1977:
1973:
1969:
1965:
1960:
1957:
1953:
1949:
1945:
1941:
1937:
1933:
1929:
1925:
1920:
1919:
1906:
1902:
1898:
1894:
1890:
1886:
1882:
1878:
1871:
1864:
1849:
1845:
1838:
1830:
1826:
1821:
1816:
1812:
1808:
1804:
1800:
1796:
1792:
1788:
1781:
1765:
1761:
1754:
1746:
1742:
1738:
1736:9780123745118
1732:
1728:
1724:
1720:
1713:
1705:
1701:
1697:
1693:
1689:
1685:
1681:
1677:
1670:
1668:
1659:
1652:
1650:
1641:
1639:0-14-025670-9
1635:
1631:
1624:
1616:
1612:
1608:
1604:
1599:
1594:
1590:
1586:
1582:
1575:
1566:
1564:
1553:
1551:
1540:
1531:
1522:
1513:
1511:
1502:
1498:
1493:
1488:
1484:
1480:
1477:(4): 278–88.
1476:
1472:
1468:
1461:
1453:
1447:
1439:
1435:
1431:
1427:
1423:
1419:
1415:
1411:
1404:
1396:
1392:
1387:
1382:
1379:(3): 406–24.
1378:
1374:
1370:
1363:
1361:
1345:
1341:
1334:
1319:
1315:
1309:
1301:
1297:
1292:
1287:
1283:
1279:
1275:
1271:
1267:
1260:
1258:
1256:
1247:
1243:
1238:
1233:
1229:
1225:
1221:
1217:
1213:
1206:
1198:
1194:
1190:
1186:
1182:
1178:
1174:
1170:
1162:
1160:
1152:. London, UK.
1151:
1147:
1140:
1132:
1128:
1124:
1120:
1116:
1112:
1109:(2): 103–12.
1108:
1104:
1103:Pain Practice
1097:
1089:
1085:
1081:
1077:
1073:
1069:
1065:
1061:
1053:
1045:
1041:
1036:
1031:
1027:
1023:
1019:
1015:
1011:
1004:
997:
996:9780123742483
993:
989:
983:
981:
979:
977:
968:
964:
960:
956:
952:
948:
944:
940:
933:
931:
922:
918:
914:
910:
906:
902:
898:
894:
887:
879:
875:
871:
867:
863:
859:
856:(2): 157–62.
855:
851:
844:
836:
832:
827:
822:
817:
812:
808:
804:
801:(4): e61926.
800:
796:
792:
785:
779:
775:
774:
767:
761:
757:
756:
749:
738:September 27,
734:on 2019-04-17
733:
729:
723:
712:September 27,
707:
701:
693:
689:
685:
681:
677:
673:
669:
665:
658:
651:
650:9780123742483
647:
643:
637:
629:
625:
621:
617:
613:
609:
605:
601:
594:
586:
582:
578:
574:
569:
564:
560:
556:
552:
545:
530:
524:
520:
511:
508:
506:
503:
501:
498:
496:
493:
491:
488:
486:
484:
480:
478:
475:
473:
470:
468:
465:
463:
460:
458:
455:
453:
450:
449:
443:
439:
430:
426:
422:
418:
415:
402:
398:
394:
391:
390:
389:
387:
377:
374:
370:
366:
356:
353:
351:
348:
347:
346:
344:
340:
336:
332:
327:
325:
313:
310:
307:
303:
300:
298:
295:
294:
293:
290:
280:
277:
274:
271:
268:
265:
263:
259:
257:
254:
252:
249:
247:
243:
239:
235:
232:
231:
225:
221:
218:
214:
210:
206:
202:
198:
192:
182:
178:
174:
170:
168:
164:
160:
156:
151:
141:
137:
133:
124:
122:
118:
114:
109:
107:
103:
99:
95:
90:
88:
84:
83:neural firing
80:
77:
73:
67:
65:
61:
57:
53:
48:
38:
32:
27:
22:
3130:
3126:
3102:(9): 801–7.
3099:
3095:
3054:
3050:
3010:
3006:
2975:
2971:
2935:(1): 68–74.
2932:
2928:
2902:(1): 46–62.
2899:
2895:
2868:
2864:
2825:
2821:
2805:
2796:
2741:
2686:
2659:
2655:
2624:
2620:
2583:
2580:Neurosurgery
2579:
2545:
2541:
2514:
2510:
2489:
2485:
2452:
2448:
2436:. Retrieved
2432:the original
2396:(1): 64–79.
2393:
2389:
2360:
2357:Muscle Nerve
2356:
2337:
2333:
2302:
2298:
2264:(9): 852–8.
2261:
2257:
2224:
2221:Brain Injury
2220:
2203:
2199:
2166:
2162:
2122:
2118:
2084:
2080:
2050:(5): 415–8.
2047:
2043:
2008:
2004:
1967:
1963:
1927:
1924:Neurosurgery
1923:
1880:
1876:
1863:
1851:. Retrieved
1847:
1837:
1794:
1790:
1780:
1768:. Retrieved
1763:
1753:
1718:
1712:
1682:(5): 515–9.
1679:
1675:
1657:
1629:
1623:
1588:
1584:
1574:
1539:
1530:
1521:
1474:
1470:
1460:
1446:
1416:(1): 63–74.
1413:
1409:
1403:
1376:
1372:
1347:. Retrieved
1343:
1333:
1322:. Retrieved
1318:the original
1308:
1273:
1269:
1219:
1215:
1205:
1172:
1168:
1149:
1139:
1106:
1102:
1096:
1063:
1059:
1052:
1020:(1): 68–74.
1017:
1013:
1003:
945:(1): 68–77.
942:
938:
896:
892:
886:
853:
849:
843:
798:
794:
784:
771:
766:
753:
748:
736:. Retrieved
732:the original
722:
710:. Retrieved
700:
667:
663:
657:
636:
603:
600:Neurosurgery
599:
593:
558:
554:
544:
532:. Retrieved
523:
505:Optogenetics
482:
440:
436:
427:
423:
419:
413:
411:
383:
375:
371:
367:
364:
328:
321:
291:
288:
222:
194:
179:
175:
171:
159:chronic pain
153:
138:
134:
130:
110:
91:
68:
64:optogenetics
46:
45:
2656:Circulation
1150:The Express
773:NCT01608061
755:NCT01559220
393:Intrathecal
163:spinal cord
79:Substance P
3184:Categories
2340:: S7–S13.
2258:PM & R
1970:: 204–11.
1853:11 October
1770:11 October
1324:2014-10-12
1222:(2): 165.
516:References
397:ziconotide
117:depression
2786:ignored (
2776:cite book
2731:ignored (
2721:cite book
2608:115231676
2438:3 October
1992:222083466
1591:(2): E1.
921:206204986
561:(5): E1.
534:1 October
485:(journal)
462:BrainGate
3147:15448578
3118:20878038
3083:23230533
3037:23450547
2994:16647594
2959:18164485
2887:25216508
2852:21422772
2828:: 1–15.
2768:17691395
2713:17691369
2643:19005196
2600:18981888
2570:35191893
2562:21992423
2533:16738284
2498:20277440
2477:26003637
2469:20842599
2420:18490925
2334:Pain Med
2321:23429927
2286:34407448
2278:19769920
2249:26677114
2241:16094783
2212:10666287
2191:13364877
2183:25180016
2147:10011197
2139:22748024
2109:30103603
2101:12378060
2064:11709646
2035:15446990
2027:17038030
1984:20633126
1944:11904018
1905:20061363
1897:24875080
1829:23579662
1766:. London
1745:19660668
1704:24246117
1696:15993077
1615:28313693
1607:20672911
1501:19305744
1438:35340441
1430:17187498
1395:23395370
1300:24177464
1246:20937936
1197:16831609
1189:25112889
1131:24008740
1123:20070547
1088:20959524
1080:25112892
1044:18164485
967:39688758
959:23340073
913:23311356
878:41394936
870:15172106
835:23620795
795:PLOS ONE
684:22947069
628:23473956
620:21716154
585:26756883
577:24175861
446:See also
401:baclofen
205:dystonia
94:epilepsy
72:dopamine
3155:2432783
3074:3514915
3028:7163280
2950:5084128
2916:9013359
2678:9537342
2411:3790898
2377:9483570
2072:1263798
1952:1081499
1820:4179459
1799:Bibcode
1492:2644491
1349:Oct 13,
1291:3809784
1237:4523130
1035:5084128
826:3631254
803:Bibcode
692:1711587
408:History
242:cochlea
76:peptide
3153:
3145:
3116:
3081:
3071:
3035:
3025:
2992:
2957:
2947:
2914:
2885:
2850:
2840:
2766:
2756:
2711:
2701:
2676:
2641:
2606:
2598:
2568:
2560:
2531:
2496:
2475:
2467:
2418:
2408:
2375:
2319:
2284:
2276:
2247:
2239:
2210:
2189:
2181:
2145:
2137:
2107:
2099:
2070:
2062:
2033:
2025:
1990:
1982:
1950:
1942:
1903:
1895:
1827:
1817:
1791:Nature
1743:
1733:
1702:
1694:
1636:
1613:
1605:
1499:
1489:
1436:
1428:
1393:
1373:Neuron
1298:
1288:
1244:
1234:
1195:
1187:
1129:
1121:
1086:
1078:
1042:
1032:
994:
965:
957:
919:
911:
876:
868:
833:
823:
690:
682:
648:
626:
618:
583:
575:
414:et al.
335:induce
121:stroke
58:), an
3151:S2CID
2604:S2CID
2566:S2CID
2473:S2CID
2373:S2CID
2282:S2CID
2245:S2CID
2187:S2CID
2159:(PDF)
2143:S2CID
2105:S2CID
2068:S2CID
2031:S2CID
1988:S2CID
1948:S2CID
1901:S2CID
1873:(PDF)
1700:S2CID
1611:S2CID
1434:S2CID
1193:S2CID
1127:S2CID
1084:S2CID
963:S2CID
917:S2CID
874:S2CID
688:S2CID
624:S2CID
581:S2CID
343:tesla
339:ionic
207:, or
35:[
3195:Pain
3143:PMID
3114:PMID
3079:PMID
3033:PMID
2990:PMID
2955:PMID
2912:PMID
2883:PMID
2848:PMID
2838:ISBN
2788:help
2764:PMID
2754:ISBN
2733:help
2709:PMID
2699:ISBN
2674:PMID
2639:PMID
2596:PMID
2558:PMID
2529:PMID
2494:PMID
2465:PMID
2440:2012
2416:PMID
2317:PMID
2274:PMID
2237:PMID
2208:PMID
2179:PMID
2163:Pain
2135:PMID
2097:PMID
2060:PMID
2023:PMID
1980:PMID
1968:1199
1940:PMID
1893:PMID
1855:2014
1825:PMID
1772:2014
1741:PMID
1731:ISBN
1692:PMID
1634:ISBN
1603:PMID
1497:PMID
1426:PMID
1391:PMID
1351:2014
1296:PMID
1242:PMID
1185:PMID
1119:PMID
1076:PMID
1040:PMID
992:ISBN
955:PMID
909:PMID
866:PMID
831:PMID
740:2013
714:2013
680:PMID
646:ISBN
616:PMID
573:PMID
536:2013
306:TENS
100:and
56:rTMS
3135:doi
3104:doi
3069:PMC
3059:doi
3023:PMC
3015:doi
2980:doi
2945:PMC
2937:doi
2904:doi
2873:doi
2830:doi
2746:doi
2691:doi
2664:doi
2629:doi
2625:359
2588:doi
2550:doi
2519:doi
2515:354
2457:doi
2406:PMC
2398:doi
2365:doi
2342:doi
2307:doi
2303:139
2266:doi
2229:doi
2171:doi
2167:155
2127:doi
2089:doi
2052:doi
2013:doi
1972:doi
1932:doi
1885:doi
1815:PMC
1807:doi
1795:496
1723:doi
1684:doi
1593:doi
1487:PMC
1479:doi
1418:doi
1381:doi
1286:PMC
1278:doi
1274:123
1232:PMC
1224:doi
1177:doi
1111:doi
1068:doi
1030:PMC
1022:doi
947:doi
901:doi
858:doi
854:363
821:PMC
811:doi
672:doi
608:doi
563:doi
333:to
244:or
3186::
3149:.
3141:.
3131:83
3129:.
3112:.
3100:42
3098:.
3094:.
3077:.
3067:.
3053:.
3049:.
3031:.
3021:.
3009:.
3005:.
2988:.
2976:31
2974:.
2970:.
2953:.
2943:.
2931:.
2927:.
2910:.
2900:14
2898:.
2881:.
2869:37
2867:.
2863:.
2846:.
2836:.
2826:24
2824:.
2820:.
2780::
2778:}}
2774:{{
2762:.
2752:.
2725::
2723:}}
2719:{{
2707:.
2697:.
2672:.
2660:97
2658:.
2654:.
2637:.
2623:.
2619:.
2602:.
2594:.
2584:63
2582:.
2564:.
2556:.
2546:14
2544:.
2527:.
2513:.
2509:.
2490:20
2488:.
2471:.
2463:.
2453:12
2451:.
2414:.
2404:.
2394:15
2392:.
2388:.
2371:.
2359:.
2336:.
2332:.
2315:.
2301:.
2297:.
2280:.
2272:.
2260:.
2243:.
2235:.
2225:19
2223:.
2204:31
2202:.
2185:.
2177:.
2165:.
2161:.
2141:.
2133:.
2123:15
2121:.
2103:.
2095:.
2085:77
2083:.
2066:.
2058:.
2048:18
2046:.
2029:.
2021:.
2009:13
2007:.
2003:.
1986:.
1978:.
1966:.
1946:.
1938:.
1928:50
1926:.
1899:.
1891:.
1881:13
1879:.
1875:.
1846:.
1823:.
1813:.
1805:.
1793:.
1789:.
1762:.
1739:.
1729:.
1698:.
1690:.
1680:12
1678:.
1666:^
1648:^
1609:.
1601:.
1589:29
1587:.
1583:.
1562:^
1549:^
1509:^
1495:.
1485:.
1473:.
1469:.
1432:.
1424:.
1412:.
1389:.
1377:77
1375:.
1371:.
1359:^
1342:.
1294:.
1284:.
1272:.
1268:.
1254:^
1240:.
1230:.
1220:68
1218:.
1214:.
1191:.
1183:.
1173:17
1171:.
1158:^
1148:.
1125:.
1117:.
1107:10
1105:.
1082:.
1074:.
1064:17
1062:.
1038:.
1028:.
1016:.
1012:.
975:^
961:.
953:.
943:20
941:.
929:^
915:.
907:.
897:16
895:.
872:.
864:.
852:.
829:.
819:.
809:.
797:.
793:.
686:.
678:.
668:16
666:.
622:.
614:.
604:69
602:.
579:.
571:.
559:35
557:.
553:.
203:,
123:.
115:,
85:,
3157:.
3137::
3120:.
3106::
3085:.
3061::
3055:3
3041:.
3039:.
3017::
3011:2
2996:.
2982::
2961:.
2939::
2933:5
2918:.
2906::
2889:.
2875::
2854:.
2832::
2790:)
2770:.
2748::
2735:)
2715:.
2693::
2680:.
2666::
2645:.
2631::
2610:.
2590::
2572:.
2552::
2535:.
2521::
2500:.
2479:.
2459::
2442:.
2422:.
2400::
2379:.
2367::
2361:6
2350:.
2344::
2338:7
2323:.
2309::
2288:.
2268::
2262:1
2251:.
2231::
2214:.
2193:.
2173::
2149:.
2129::
2111:.
2091::
2074:.
2054::
2037:.
2015::
1994:.
1974::
1954:.
1934::
1907:.
1887::
1857:.
1831:.
1809::
1801::
1774:.
1747:.
1725::
1706:.
1686::
1642:.
1617:.
1595::
1503:.
1481::
1475:5
1440:.
1420::
1414:7
1397:.
1383::
1353:.
1327:.
1302:.
1280::
1248:.
1226::
1199:.
1179::
1133:.
1113::
1090:.
1070::
1046:.
1024::
1018:5
998:.
969:.
949::
923:.
903::
880:.
860::
837:.
813::
805::
799:8
742:.
716:.
694:.
674::
652:.
630:.
610::
587:.
565::
538:.
39:]
23:.
Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.