Neuromodulation (medicine)

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This article is about the therapeutic electromagnetic or chemical stimulation of nerve cells. For the natural physiological process in the nervous system, see Neuromodulation (biology).

Neuromodulation, defined by the International Neuromodulation Society as “the alteration of nerve activity through the delivery of electrical stimulation or chemical agents to targeted sites of the body,” is carried out to normalize – or modulate – nerve function. Neuromodulation can involve a range of electromagnetic stimuli such as a strong magnetic field (repetitive transcranial magnetic stimulation), a very small electric current or, potentially, light (optogenetics).[1]

Electrical stimulation using implantable devices, also known as neurostimulation, came into modern usage in the 1980s and its techniques and applications have continued to develop and expand.[2] The therapy employs the body’s natural biological response by stimulating nerve cell activity that can influence populations of nerves by releasing transmitters, such as dopamine, or other chemical messengers such as the peptide Substance P, that can modulate the excitability and firing patterns of neural circuits.

Spinal cord stimulation[edit]

A form of neuromodulation therapy in common use since the 1980s is spinal cord stimulation, a reversible, non-pharmacological therapy for chronic pain management that delivers mild electrical pulses to the spinal cord.[3] 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 cardiac pacemaker, 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.[4]

Deep brain stimulation[edit]

Another commonly used neuromodulation treatment developed in the 1980s is deep brain stimulation, which may be used to help limit symptoms of movement disorder in Parkinson's disease, dystonia, or essential tremor.[5]

Other applications of neuromodulation therapy[edit]

Existing and emerging neuromodulation treatments also include application in medication-resistant epilepsy,[6] chronic head pain conditions, and functional therapy ranging from bladder and bowel or respiratory control to improvement of sensory deficits, such as hearing (cochlear implants and auditory brainstem implants) and vision (retinal implants).[7] Technical improvements include a trend toward minimally invasive (or noninvasive) systems; as well as smaller, more sophisticated devices that may have automated feedback control,[8] and conditional compatibility with magnetic resonance imaging.[9][10]

Neuromodulation therapy has been investigated for other chronic, neurologically based conditions, such as Alzheimer's disease[11][12] and as an adjunctive treatment in recovery from stroke.[13][14]

Some types of neuromodulation, and their usual acronyms,[1] are:

See also[edit]


  1. ^ a b "International Neuromodulation Society home page". Retrieved 1 October 2013. 
  2. ^ Krames, Elliot S.; Peckham, P. Hunter; Rezai, Ali R., eds. (2009). Neuromodulation, Vol. 1-2. Academic Press. pp. 1–1200. ISBN 9780123742483.
  3. ^ Mekhail NA, Cheng J, Narouze S, Kapural L, Mekhail MN, Deer T. Clinical applications of neurostimulation: forty years later. Pain Pract. 2010;10(2):103-112.
  4. ^ Bailey, Madeleine. "A remote control turns off my spine", London, UK. The Express. May 14, 2013.
  5. ^ Bronstein, JM.; Tagliati, M.; Alterman, RL.; Lozano, AM.; Volkmann, J.; Stefani, A.; Horak, FB.; Okun, MS. et al. (Feb 2011). "Deep brain stimulation for Parkinson disease: an expert consensus and review of key issues.". Arch Neurol 68 (2): 165. doi:10.1001/archneurol.2010.260. PMID 20937936. 
  6. ^ Al-Otaibi, FA.; Hamani, C.; Lozano, AM. (Oct 2011). "Neuromodulation in epilepsy.". Neurosurgery 69 (4): 957–79; discussion 979. doi:10.1227/NEU.0b013e31822b30cd. PMID 21716154. 
  7. ^ Krames, Elliot S.; Peckham, P. Hunter; Rezai, Ali R., eds. (2009). Neuromodulation, Vol. 1-2. Academic Press. p. 274. ISBN 9780123742483.
  8. ^ Wu, C. and Sharan, A. D. (2013), Neurostimulation for the Treatment of Epilepsy: A Review of Current Surgical Interventions. Neuromodulation: Technology at the Neural Interface, 16: 10–24. doi:10.1111/j.1525-1403.2012.00501.x PMID 22947069
  9. ^ Boston Scientific Corporation, "Precision™ Plus Spinal Cord Stimulator System Receives CE Mark Approval as MRI Conditional", Paris, France. August 28, 2012. Retrieved September 27, 2013.
  10. ^ Medtronic, Inc. "Medtronic Introduces the First and Only Neurostimulation Systems for Chronic Pain Designed for Full-Body MRI Safety*", Minneapolis, MN. August 6, 2013. Retrieved September 27, 2013.
  11. ^ Rezai A, The Ohio State University. Deep Brain Stimulation for the Treatment of Alzheimer's Disease. In: [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2013 Sept 27]. Available from: NLM Identifier: NCT01559220.
  12. ^ Functional Neuromodulation Ltd. ADvance DBS-f in Patients With Mild Probable Alzheimer's Disease. In: [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2013 Sept 27]. Available from: NLM Identifier: NCT01608061.
  13. ^ Matsumura, Y.; Hirayama, T.; Yamamoto, T. (2013). "Comparison between pharmacologic evaluation and repetitive transcranial magnetic stimulation-induced analgesia in poststroke pain patients.". Neuromodulation 16 (4): 349–54; discussion 354. doi:10.1111/ner.12019. PMID 23311356. 
  14. ^ a b Feng, WW.; Bowden, MG.; Kautz, S. "Review of transcranial direct current stimulation in poststroke recovery.". Top Stroke Rehabil 20 (1): 68–77. doi:10.1310/tsr2001-68. PMID 23340073. 
  15. ^ Lega, BC.; Halpern, CH.; Jaggi, JL.; Baltuch, GH. (Jun 2010). "Deep brain stimulation in the treatment of refractory epilepsy: update on current data and future directions.". Neurobiol Dis 38 (3): 354–60. doi:10.1016/j.nbd.2009.07.007. PMID 19631750. 
  16. ^ FDA "Premarket Approval (PMA) Inspire II Upper Airway Stimulation System" U.S. Food and Drug Administration. April 30, 2014.
  17. ^ George, MS.; Nahas, Z.; Borckardt, JJ.; Anderson, B.; Burns, C.; Kose, S.; Short, EB. (Jan 2007). "Vagus nerve stimulation for the treatment of depression and other neuropsychiatric disorders.". Expert Rev Neurother 7 (1): 63–74. doi:10.1586/14737175.7.1.63. PMID 17187498. 

Further reading[edit]

  1. Aló, KM.; Holsheimer, J. (Apr 2002). "New trends in neuromodulation for the management of neuropathic pain.". Neurosurgery 50 (4): 690–703; discussion 703–4. doi:10.1097/00006123-200204000-00003. PMID 11904018. 
  2. 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.
  3. Andrews, RJ. (Jun 2010). "Neuromodulation: advances in the next five years.". Ann N Y Acad Sci 1199: 204–11. doi:10.1111/j.1749-6632.2009.05379.x. PMID 20633126. 
  4. Attal, N.; Cruccu, G.; Haanpää, M.; Hansson, P.; Jensen, TS.; Nurmikko, T.; Sampaio, C.; Sindrup, S.; Wiffen, P. (Nov 2006). "EFNS guidelines on pharmacological treatment of neuropathic pain.". Eur J Neurol 13 (11): 1153–69. doi:10.1111/j.1468-1331.2006.01511.x. PMID 17038030. 
  5. Ben-Menachem, E. (Sep 2001). "Vagus nerve stimulation, side effects, and long-term safety.". J Clin Neurophysiol 18 (5): 415–8. doi:10.1097/00004691-200109000-00005. PMID 11709646. 
  6. Beric, A.; Kelly, PJ.; Rezai, A.; Sterio, D.; Mogilner, A.; Zonenshayn, M.; Kopell, B. (2001). "Complications of deep brain stimulation surgery.". Stereotact Funct Neurosurg 77 (1-4): 73–8. doi:10.1159/000064600. PMID 12378060. 
  7. Deer, T. R., Prager, J., Levy, R., Rathmell, J., Buchser, E., Burton, A., Caraway, D., Cousins, M., De Andrés, J., Diwan, S., Erdek, M., Grigsby, E., Huntoon, M., Jacobs, M. S., Kim, P., Kumar, K., Leong, M., Liem, L., McDowell II, G. C., Panchal, S., Rauck, R., Saulino, M., Sitzman, B. T., Staats, P., Stanton-Hicks, M., Stearns, L., Wallace, M., Willis, K. D., Witt, W., Yaksh, T. and Mekhail, N. (2012), Polyanalgesic Consensus Conference 2012: Recommendations for the Management of Pain by Intrathecal (Intraspinal) Drug Delivery: Report of an Interdisciplinary Expert Panel. Neuromodulation: Technology at the Neural Interface, 15: 436–466.
  8. Dormandy JA, Rutherford RB. Management of peripheral arterial disease (PAD). TASC Working Group. TransAtlantic Inter-Society Consensus (TASC). J Vasc Surg. 2000;31(1 pt 2):S1–S296.
  9. Francisco GE, Hu MM, Boake C, Ivanhoe CB. Efficacy of early use of intrathecal baclofen therapy for treating spastic hypertonia due to acquired brain injury. Brain Inj. 2005 May;19(5):359-64.
  10. Francisco GE, Saulino MF, Yablon SA, Turner M. Intrathecal baclofen therapy: an update. PM R. 2009 Sep;1(9):852-8
  11. Gaylor JM, Raman G, Chung M, Lee J, Rao M, Lau J, Poe DS. Cochlear Implantation in Adults. A Systematic Review and Meta-analysis. JAMA Otolaryngol Head Neck Surg. 2013;139(3):265-272.
  12. Gildenberg PL: History of electrical neuromodulation for chronic pain. Pain Med 2006;7:S7-S13
  13. Gracies JM, Nance P, Elovic E, McGuire J, Simpson DM (1997) Traditional pharmacological treatments for spacticity part I: local treatments. Muscle Nerve Suppl 6: S1–S92
  14. Greenberg BD, Gabriels LA, Malone DA Jr, Rezai AR, Friehs GM, Okun MS, Shapira NA, Foote KD, Cosyns PR, Kubu CS, Malloy PF, Salloway SP, Giftakis JE, Rise MT, Machado AG, Baker KB, Stypulkowski PH, Goodman WK, Rasmussen SA, Nuttin BJ. Deep brain stimulation of the ventral internal capsule/ventral striatum for obsessive-compulsive disorder: worldwide experience. Mol Psychiatry. 2010 Jan;15(1):64-79.
  15. Health C for D and R. Recently-Approved Devices - VNS Therapy System - P970003s050. Available at: Accessed October 3, 2012.
  16. Jobst, BC. (Sep 2010). "Electrical stimulation in epilepsy: vagus nerve and brain stimulation.". Curr Treat Options Neurol 12 (5): 443–53. doi:10.1007/s11940-010-0087-4. PMID 20842599. 
  17. Kellaway P: The part played by electric fish in the early history of bioelectricity and electrotherapy. Bull Hist Med 1946;20:112-137
  18. Krames E et al. Using the SAFE principles when evaluating electrical stimulation therapies for the pain of failed back surgery syndrome. Neuromodulation 2011;14:299–311.
  19. Mallet L, Polosan M, Jaafari N, Baup N, Welter ML, Fontaine D, du Montcel ST, Yelnik J, Chéreau I, Arbus C, Raoul S, Aouizerate B, Damier P, Chabardès S, Czernecki V, Ardouin C, Krebs MO, Bardinet E, Chaynes P, Burbaud P, Cornu P, Derost P, Bougerol T, Bataille B, Mattei V, Dormont D, Devaux B, Vérin M, Houeto JL, Pollak P, Benabid AL, Agid Y, Krack P, Millet B, Pelissolo A; STOC Study Group. Subthalamic nucleus stimulation in severe obsessive-compulsive disorder. N Engl J Med. 2008 Nov 13;359(20):2121-34.
  20. Petropoulou KB, Panourias IG, Rapidi C-A, and Sakas DE. The phenomenon of spasticity: a pathophysiological and clinical introduction to neuromodulation therapies. Acta Neurochir Suppl (2007) 97(1): 137–144.
  21. Ratto, C., et al., Sacral neuromodulation in the treatment of defecation disorders. Acta Neurochir Suppl, 2007. 97(Pt 1): p. 341-50.
  22. Sakas DE, Simpson BA, Krames ES (eds). Operative Neuromodulation Acta Neurochirurgica Supplements: An introduction to operative neuromodulation and functional neuroprosthetics, the new frontiers of clinical neuroscience and biotechnology. Vienna Springer 2007. 482 p.
  23. Schachter, S. C., & Schmidt, D. (2003). Introduction. In Vagus Nerve Stimulation. (2nd ed.). (p. x). London, United Kingdom: Martin Dunitz.
  24. Sharan AD, Rezai AR. Neurostimulation for Epilepsy. In: Krames ES, Peckham HP, Rezai AR, eds. Neuromodulation. London: Elsevier; 2009:617–66.
  25. Slavin KV (ed): Peripheral Nerve Stimulation. Prog Neurol Surg. Basel, Karger, 2011, vol 24, 224 p.
  26. Stanton-Hicks M, Salamon J: Stimulation of the central and peripheral nervous system for the control of pain. J Clin Neurophysiol 1997;14:46-62.
  27. Sun, FT.; Morrell, MJ.; Wharen, RE. (Jan 2008). "Responsive cortical stimulation for the treatment of epilepsy.". Neurotherapeutics 5 (1): 68–74. doi:10.1016/j.nurt.2007.10.069. PMID 18164485. 
  28. Ubbink DT, Vermeulen H. Spinal Cord Stimulation for Critical Leg Ischemia: A Review of Effectiveness and Optimal Patient Selection. Journal of Pain and Symptom Management 2006;31(4):S30-S35.
  29. Ubbink DT, Vermeulen H. Spinal cord stimulation for non-reconstructable chronic critical leg ischemia. Cochrane Database of Systematic Reviews 2005.
  30. Yampolsky C, Hem S, Bendersky D. Dorsal column stimulator applications. Surg Neurol Int. 2012;3(Suppl 4):S275-89. doi: 10.4103/2152-7806.103019. Epub 2012 Oct 31. Accessed November 3, 2013.
  31. Yelnik, AP.; Simon, O.; Parratte, B.; Gracies, JM. (Oct 2010). "How to clinically assess and treat muscle overactivity in spastic paresis.". J Rehabil Med 42 (9): 801–7. doi:10.2340/16501977-0613. PMID 20878038. 
  32. Zafonte R, Lombard L, Elovic E (2004) Antispasticity medications: uses and limitations of enteral therapy. Am J Phys Med Rehabil 83:S50–S58

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