Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Invasive brain stimulation for the treatment of neuropathic pain

Abstract

Neurostimulation therapy is indicated for neuropathic pain that is refractory to medical treatment, and includes stimulation of the dorsal spinal cord, deep brain structures, and the precentral motor cortex. Spinal cord stimulation is validated in the treatment of selected types of chronic pain syndromes, such as failed back surgery syndrome. Deep brain stimulation (DBS) has shown promise as a treatment for peripheral neuropathic pain and phantom limb pain. Compared with DBS, motor cortex stimulation (MCS) is currently more frequently used, mainly because it is more easily performed, and has a wider range of indications (including central poststroke pain). Controlled trials have demonstrated the efficacy of MCS in the treatment of various types of neuropathic pain, although these trials included a limited number of patients and need to be confirmed by large, controlled, multicenter studies. Despite technical progress in neurosurgical navigation, results from studies of MCS are variable, and validated criteria for selecting good candidates for implantation are lacking. However, the evidence in favor of MCS is sufficient to include it in the range of therapeutic options for refractory neuropathic pain. In this Review, the respective efficacies and mechanisms of action of DBS and MCS are discussed.

Key Points

  • Neurostimulation therapy is indicated for drug-resistant neuropathic pain

  • Neurostimulation therapy for pain mainly includes spinal cord stimulation, deep brain stimulation, and motor cortex stimulation

  • Motor cortex stimulation is more easily performed and has currently a wider range of indications than deep brain stimulation

  • The efficacy of motor cortex stimulation has been demonstrated in the treatment of neuropathic pain by a small number of controlled trials

  • The criteria for selecting good candidates for deep brain or motor cortex stimulation still remain to be clearly delineated

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Three-dimensional images of the brain reconstructed from MRI scans, depicted without the superficial layers of the cortex.
Figure 2: Mechanism of action of epidural electrical stimulation or TMS of the cortex.
Figure 3: Restoration of intracortical inhibition using rTMS of the motor cortex corresponding to a painful hand.
Figure 4: Comparison of on-stimulation and off-stimulation outcomes in patients undergoing MCS.

Similar content being viewed by others

References

  1. Merskey, H. & Bogduk, N. in Classification of Chronic Pain (International Association for the Study of Pain, Seattle, 1994).

    Google Scholar 

  2. Treede, R. D. et al. Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neurology 70, 1630–1635 (2008).

    Article  CAS  PubMed  Google Scholar 

  3. Gilron, I., Watson, C. P., Cahill, C. M. & Moulin, D. E. Neuropathic pain: a practical guide for the clinician. CMAJ 175, 265–275 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  4. Attal, N. et al. EFNS guidelines on pharmacological treatment of neuropathic pain. Eur. J. Neurol. 13, 1153–1169 (2006).

    Article  CAS  PubMed  Google Scholar 

  5. Dworkin, R. H. et al. Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain 132, 237–251 (2007).

    Article  CAS  PubMed  Google Scholar 

  6. Namaka, M. et al. A treatment algorithm for neuropathic pain: an update. Consult. Pharm. 24, 885–902 (2009).

    Article  PubMed  Google Scholar 

  7. Finnerup, N. B., Sindrup, S. H. & Jensen, T. S. The evidence for pharmacological treatment of neuropathic pain. Pain 150, 573–581 (2010).

    Article  PubMed  Google Scholar 

  8. Aichaoui, F., Mertens, P. & Sindou, M. Dorsal root entry zone lesioning for pain after brachial plexus avulsion: Results with special emphasis on differential effects on the paroxysmal versus the continuous components. A prospective study in a 29-patient consecutive series. Pain 152, 1932–1930 (2011).

    Article  Google Scholar 

  9. Ali, M. et al. Differential efficacy of electrical motor cortex stimulation and lesioning of the dorsal root entry zone for continuous versus paroxysmal pain after brachial plexus avulsion. Neurosurgery 65, 1252–1258 (2011).

    Article  Google Scholar 

  10. Cruccu, G. et al. EFNS guidelines on neurostimulation therapy for neuropathic pain. Eur. J. Neurol. 14, 952–970 (2007).

    Article  CAS  PubMed  Google Scholar 

  11. Lefaucheur, J. P. The use of repetitive transcranial magnetic stimulation (rTMS) in chronic neuropathic pain. Neurophysiol. Clin. 36, 117–124 (2006).

    Article  CAS  PubMed  Google Scholar 

  12. Lefaucheur, J. P. et al. The use of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) to relieve pain. Brain Stimul. 1, 337–344 (2008).

    Article  PubMed  Google Scholar 

  13. Lefaucheur, J. P. Use of repetitive transcranial magnetic stimulation in pain relief. Expert Rev. Neurother. 8, 799–808 (2008).

    Article  PubMed  Google Scholar 

  14. Katayama, Y., Yamamoto, T., Kobayashi, K., Kasai, M., Oshima, H. & Fukaya, C. Motor cortex stimulation for post-stroke pain: comparison of spinal cord and thalamic stimulation. Stereotact. Funct. Neurosurg. 77, 183–186 (2001).

    Article  CAS  PubMed  Google Scholar 

  15. Canavero, S. & Bonicalzi, V. Spinal cord stimulation for central pain. Pain 103, 225–226 (2003).

    Article  PubMed  Google Scholar 

  16. Aly, M. M. et al. Spinal cord stimulation for central poststroke pain. Neurosurgery 67 (Suppl.), 206–212 (2010).

    Google Scholar 

  17. Canavero, S. & Bonicalzi, V. in Central Pain Syndrome, 2nd edn (Cambridge University Press, New York, 2011).

    Book  Google Scholar 

  18. Heath, R. G. & Mickle, W. A. Evaluation of seven years' experience with depth electrode studies in human patients, in Electrical Studies on the Unanesthetized Brain (eds Ramey, E. R. & O'Doherty, D. S.) 214–247 (Paul B. Hoeber, New York, 1960).

    Google Scholar 

  19. Melzack, R. & Wall, P. D. Pain mechanisms: a new theory. Science 150, 971–979 (1965).

    Article  CAS  PubMed  Google Scholar 

  20. Nashold, B. S. Jr & Friedman, H. Dorsal column stimulation for control of pain. Preliminary report on 30 patients. J. Neurosurg. 36, 590–597 (1972).

    Article  PubMed  Google Scholar 

  21. Hosobuchi, Y., Adams, J. E. & Rutkin, B. Chronic thalamic stimulation for the control of facial anesthesia dolorosa. Arch. Neurol. 29, 158–161 (1973).

    Article  CAS  PubMed  Google Scholar 

  22. Adams, J. E., Hosobuchi, Y. & Fields, H. L. Stimulation of internal capsule for relief of chronic pain. J. Neurosurg. 41, 740–744 (1974).

    Article  CAS  PubMed  Google Scholar 

  23. Hosobuchi, Y., Adams, J. E. & Linchitz, R. Pain relief by electrical stimulation of the central gray matter in humans and its reversal by naloxone. Science 197, 183–186 (1977).

    Article  CAS  PubMed  Google Scholar 

  24. Richardson, D. E. & Akil, H. Long term results of periventricular gray self-stimulation. Neurosurgery 1, 199–202 (1977).

    Article  CAS  PubMed  Google Scholar 

  25. Akil, H., Richardson, D. E., Barchas, J. D. & Li, C. H. Appearance of β-endorphin-like immunoreactivity in human ventricular cerebrospinal fluid upon analgesic electrical stimulation. Proc. Natl Acad. Sci. USA. 75, 5170–5172 (1978).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Akil, H., Richardson, D. E., Hughes, J. & Barchas, J. D. Enkephalin-like material elevated in ventricular cerebrospinal fluid of pain patients after analgetic focal stimulation. Science 201, 463–465 (1978).

    Article  CAS  PubMed  Google Scholar 

  27. Hosobuchi, Y., Rossier, J., Bloom, F. E. & Guillemin, R. Stimulation of human periaqueductal gray for pain relief increases immunoreactive β-endorphin in ventricular fluid. Science 203, 279–281 (1979).

    Article  CAS  PubMed  Google Scholar 

  28. Dionne, R. A. et al. Contrast medium causes the apparent increase in β-endorphin levels in human cerebrospinal fluid following brain stimulation. Pain 20, 313–321 (1984).

    Article  CAS  PubMed  Google Scholar 

  29. Hosobuchi, Y. Dorsal periaqueductal gray-matter stimulation in humans. Pacing Clin. Electrophysiol. 10, 213–216 (1987).

    Article  CAS  PubMed  Google Scholar 

  30. Young, R. F. & Chambi, V. I. Pain relief by electrical stimulation of the periaqueductal and periventricular gray matter. Evidence for a non-opioid mechanism. J. Neurosurg. 66, 364–371 (1987).

    Article  CAS  PubMed  Google Scholar 

  31. Young, R. F., Bach, F. W., Van Norman, A. S. & Yaksh, T. L. Release of β-endorphin and methionine–enkephalin into cerebrospinal fluid during deep brain stimulation for chronic pain. Effects of stimulation locus and site of sampling. J. Neurosurg. 79, 816–825 (1993).

    Article  CAS  PubMed  Google Scholar 

  32. Head, H. & Holmes, G. Sensory disturbances from cerebral lesions. Brain 34, 102–254 (1911).

    Article  Google Scholar 

  33. Vilela Filho, O. Thalamic ventrobasal stimulation for pain relief. Probable mechanisms, pathways and neurotransmitters. Arq. Neuropsiquiatr. 52, 578–584 (1994).

    Article  CAS  PubMed  Google Scholar 

  34. Nandi, D., Aziz, T., Carter, H. & Stein, J. Thalamic field potentials in chronic central pain treated by periventricular gray stimulation—a series of eight cases. Pain 101, 97–107 (2003).

    Article  PubMed  Google Scholar 

  35. Mazars, G., Merienne, L. & Cioloca, C. Treatment of certain types of pain by implantable thalamic stimulators. Neurochirurgie 20, 117–124 (1974).

    CAS  PubMed  Google Scholar 

  36. Mazars, G. Intermittent stimulation of nucleus ventralis posterolateralis for intractable pain. Surg. Neurol. 4, 93–95 (1975).

    CAS  PubMed  Google Scholar 

  37. Bittar, R. G. et al. Deep brain stimulation for pain relief: a meta-analysis. J. Clin. Neurosci. 12, 515–519 (2005).

    Article  PubMed  Google Scholar 

  38. Levy, R. M., Lamb, S. & Adams, J. E. Treatment of chronic pain by deep brain stimulation: long term follow-up and review of the literature. Neurosurgery 21, 885–893 (1987).

    Article  CAS  PubMed  Google Scholar 

  39. Kumar, K., Wyant, G. M. & Nath, R. Deep brain stimulation for control of intractable pain in humans, present and future: a ten-year follow-up. Neurosurgery 26, 774–782 (1990).

    Article  CAS  PubMed  Google Scholar 

  40. Kumar, K., Toth, C. & Nath, R. K. Deep brain stimulation for intractable pain: a 15-year experience. Neurosurgery 40, 736–747 (1997).

    Article  CAS  PubMed  Google Scholar 

  41. Rasche, D., Rinaldi, P. C., Young, R. F. & Tronnier, V. M. Deep brain stimulation for the treatment of various chronic pain syndromes. Neurosurg. Focus 21, E8 (2006).

    Article  PubMed  Google Scholar 

  42. Siegfried, J. Sensory thalamic neurostimulation for chronic pain. Pacing Clin. Electrophysiol. 10, 209–212 (1987).

    Article  CAS  PubMed  Google Scholar 

  43. Owen, S. L., Green, A. L., Stein, J. F. & Aziz, T. Z. Deep brain stimulation for the alleviation of post-stroke neuropathic pain. Pain 120, 202–206 (2006).

    Article  PubMed  Google Scholar 

  44. Bittar, R. G., Otero, S., Carter, H. & Aziz, T. Z. Deep brain stimulation for phantom limb pain. J. Clin. Neurosci. 12, 399–404 (2005).

    Article  PubMed  Google Scholar 

  45. Owen, S. L., Green, A. L., Nandi, D. D., Bittar, R. G., Wang, S. & Aziz, T. Z. Deep brain stimulation for neuropathic pain. Acta Neurochir. Suppl. 97, 111–116 (2007).

    Article  CAS  PubMed  Google Scholar 

  46. Levy, R., Deer, T. R. & Henderson, J. Intracranial neurostimulation for pain control: a review. Pain Physician 13, 157–165 (2010).

    PubMed  Google Scholar 

  47. Hamani, C. et al. Deep brain stimulation for chronic neuropathic pain: long-term outcome and the incidence of insertional effect. Pain 125, 188–196 (2006).

    Article  PubMed  Google Scholar 

  48. Coffey, R. J. Deep brain stimulation for chronic pain: results of two multicenter trials and a structured review. Pain Med. 2, 183–192 (2001).

    Article  CAS  PubMed  Google Scholar 

  49. Tsubokawa, T., Katayama, Y., Yamamoto, T., Hirayama, T. & Koyama, S. Chronic motor cortex stimulation for the treatment of central pain. Acta Neurochir. Suppl. 52, 137–139 (1991).

    Article  CAS  PubMed  Google Scholar 

  50. Tsubokawa, T., Katayama, Y., Yamamoto, T., Hirayama, T. & Koyama, S. Chronic motor cortex stimulation in patients with thalamic pain. J. Neurosurg. 78, 393–401 (1993).

    Article  CAS  PubMed  Google Scholar 

  51. Meyerson, B. A., Lindblom, U., Lind, G. & Herregodts, P. Motor cortex stimulation as treatment of trigeminal neuropathic pain. Acta Neurochir. Suppl. 58, 150–153 (1993).

    CAS  PubMed  Google Scholar 

  52. Canavero, S. Cortical stimulation for central pain. J. Neurosurg. 83, 1117 (1995).

    CAS  PubMed  Google Scholar 

  53. Canavero, S. & Bonicalzi, V. Therapeutic extradural cortical stimulation for central and neuropathic pain: a review. Clin. J. Pain 18, 48–55 (2002).

    Article  PubMed  Google Scholar 

  54. Carroll, D. et al. Motor cortex stimulation for chronic neuropathic pain: a preliminary study of 10 cases. Pain 84, 431–437 (2000).

    Article  CAS  PubMed  Google Scholar 

  55. Ebel, H., Rust, D., Tronnier, V., Böker, D. & Kunze, S. Chronic precentral stimulation in trigeminal neuropathic pain. Acta Neurochir. 138, 1300–1306 (1996).

    Article  CAS  PubMed  Google Scholar 

  56. Garcia-Larrea, L. et al. Electrical stimulation of motor cortex for pain control: a combined PET-scan and electrophysiological study. Pain 83, 259–273 (1999).

    Article  CAS  PubMed  Google Scholar 

  57. Herregodts, P., Stadnik, T., De Ridder, F. & D'Haens, J. Cortical stimulation for central neuropathic pain: 3-D surface MRI for easy determination of the motor cortex. Acta Neurochir. Suppl. 64, 132–135 (1995).

    Article  CAS  PubMed  Google Scholar 

  58. Hosomi, K. et al. Electrical stimulation of primary motor cortex within the central sulcus for intractable neuropathic pain. Clin. Neurophysiol. 119, 993–1001 (2008).

    Article  PubMed  Google Scholar 

  59. Katayama, Y., Fukaya, C. & Yamamoto, T. Poststroke pain control by chronic motor cortex stimulation: neurological characteristics predicting a favorable response. J. Neurosurg. 89, 585–591 (1998).

    Article  CAS  PubMed  Google Scholar 

  60. Katayama, Y. et al. Motor cortex stimulation for phantom limb pain: a comprehensive therapy with spinal cord and thalamic stimulation. Stereotact. Funct. Neurosurg. 77, 159–161 (2001).

    Article  CAS  PubMed  Google Scholar 

  61. Katayama, Y., Yamamoto, T., Kobayashi, K., Oshima, H. & Fukaya, C. Deep brain and motor cortex stimulation for post-stroke movement disorders and post-stroke pain. Acta Neurosurg. 87, 121–123 (2003).

    CAS  Google Scholar 

  62. Mertens, P. et al. Precentral cortex stimulation for the treatment of central neuropathic pain. Stereotact. Funct. Neurosurg. 73, 122–125 (1999).

    Article  CAS  PubMed  Google Scholar 

  63. Mogilner, A. Y. & Rezai, A. R. Epidural motor cortex stimulation with functional imaging guidance. Neurosurg. Focus 11, 4 (2001).

    Article  Google Scholar 

  64. Nguyen, J. P. et al. Treatment of deafferentation pain by chronic motor cortex stimulation: report of a series of 20 cases. Acta Neurochir. Suppl. 68, 54–60 (1997).

    CAS  PubMed  Google Scholar 

  65. Nguyen, J. P. et al. Chronic motor cortex stimulation in the treatment of central and neuropathic pain. Correlations between clinical, electrophysiological and anatomical data. Pain 82, 245–251 (1999).

    Article  CAS  PubMed  Google Scholar 

  66. Nguyen, J. P., Lefaucheur, J. P. & Keravel, Y. Motor cortex stimulation, in Electrical Stimulation and the Relief of Pain. Pain Research and Clinical Management (ed. Simpson, B. A.) 197–209 (Elsevier Science, Amsterdam, 2003).

    Google Scholar 

  67. Nuti, C. et al. Motor cortex stimulation for refractory neuropathic pain: four year outcome and predictors of efficacy. Pain 118, 43–52 (2005).

    Article  PubMed  Google Scholar 

  68. Peyron, R. et al. Electrical stimulation of precentral cortical area in the treatment of central pain: electrophysiological and PET study. Pain 62, 275–286 (1995).

    Article  CAS  PubMed  Google Scholar 

  69. Pirotte, B. et al. Comparison of functional MR imaging guidance to electrical cortical mapping for targeting selective motor cortex areas in neuropathic pain: a study based on intraoperative stereotactic navigation. AJNR Am. J. Neuroradiol. 26, 2256–2266 (2005).

    PubMed  PubMed Central  Google Scholar 

  70. Rainov, N. G., Fels, C., Heidecke, V. & Burkert, W. Epidural electrical motor cortex stimulation in patients with facial neuralgia. Clin. Neurol. Neurosurg. 99, 205–209 (1997).

    Article  CAS  PubMed  Google Scholar 

  71. Roux., F. E., Ibarrola, D., Lazorthes, Y. & Berry, I. Chronic motor cortex stimulation for phantom limb pain: a functional magnetic resonance imaging study: technical case report. Neurosurgery 48, 681–688 (2001).

    Article  CAS  PubMed  Google Scholar 

  72. Saitoh, Y. et al. Motor cortex stimulation for central and peripheral deafferentation pain. J. Neurosurg. 92, 150–155 (2000).

    Article  CAS  PubMed  Google Scholar 

  73. Saitoh, Y. et al. Motor cortex stimulation for deafferentation pain. Neurosurg. Focus 11, 1 (2001).

    Article  Google Scholar 

  74. Saitoh, Y. et al. Primary motor cortex stimulation within the central sulcus for treating deafferentation pain. Acta Neurochir. 87, 149–152 (2003).

    CAS  Google Scholar 

  75. Smith, H. et al. Motor cortex stimulation for neuropathic pain. Neurosurg. Focus 11, 2 (2001).

    Article  Google Scholar 

  76. Sol., J. C. et al. Chronic motor cortex stimulation for phantom limb pain: correlations between pain relief and functional imaging studies. Stereotact. Funct. Neurosurg. 77, 172–176 (2001).

    Article  CAS  PubMed  Google Scholar 

  77. Son, B. C., Kim, M. C., Moon, D. E. & Kang, J. K. Motor cortex stimulation in a patient with intractable complex regional pain syndrome type II with hemibody involvement. J. Neurosurg. 98, 175–179 (2003).

    Article  PubMed  Google Scholar 

  78. Tani, N., Saitoh, Y., Hirata, M., Kato, A. & Yoshimine, T. Bilateral cortical stimulation for deafferentation pain after spinal cord injury. Case report. J. Neurosurg. 101, 687–689 (2004).

    Article  PubMed  Google Scholar 

  79. Tirakotai, W. et al. Image-guided motor cortex stimulation in patients with central pain. Minim. Invasive Neurosurg. 47, 273–277 (2004).

    Article  CAS  PubMed  Google Scholar 

  80. Yamamoto, T., Katayama, Y., Hirayama, T. & Tsubokawa, T. Pharmacological classification of central post-stroke pain: comparison with the results of chronic motor cortex stimulation therapy. Pain 72, 5–12 (1997).

    Article  CAS  PubMed  Google Scholar 

  81. De Ridder, D., De Mulder, G., Verstraeten, E., Sunaert, S. & Moller, A. Somatosensory cortex stimulation for deafferentation pain. Acta Neurochir. Suppl. 97, 67–74 (2007).

    Article  CAS  PubMed  Google Scholar 

  82. Kuroda, R. et al. Somatosensory cortex stimulation-evoked analgesia in rats: potentiation by NO synthase inhibition. Life Sci. 66, PL271–PL276 (2000).

    Article  CAS  PubMed  Google Scholar 

  83. Hirayama, A. et al. Reduction of intractable deafferentation pain by navigation-guided repetitive transcranial magnetic stimulation of the primary motor cortex. Pain 122, 22–27 (2006).

    Article  PubMed  Google Scholar 

  84. Brodmann, K. in Vergleichende Lokalisationslehre der Grosshirnrinde in Prinzipien dargestellt auf Grund des Zellenbaues (Johann Ambrosius Barth, Leipzig, 1925).

    Google Scholar 

  85. Penfield, W. & Rasmussen, T. in The Cerebral Cortex of Man. A Clinical Study of Localization of Function (Macmillan, New York, 1950).

    Google Scholar 

  86. Rao, S. M. et al. Somatotopic mapping of the human primary motor cortex with functional magnetic resonance imaging. Neurology 45, 919–924 (1995).

    Article  CAS  PubMed  Google Scholar 

  87. Pirotte, B. et al. Combination of functional magnetic resonance imaging-guided neuronavigation and intraoperative cortical brain mapping improves targeting of motor cortex stimulation in neuropathic pain. Neurosurgery 56, 344–359 (2005).

    PubMed  Google Scholar 

  88. Lefaucheur, J. P. & de Andrade, D. C. Intraoperative neurophysiologic mapping of the central cortical region for epidural electrode placement in the treatment of neuropathic pain by motor cortex stimulation. Brain Stimul. 2, 138–148 (2009).

    Article  PubMed  Google Scholar 

  89. Woolsey, C. N., Erickson, T. C. & Gilson, W. E. Localization in somatic sensory and motor areas of human cerebral cortex as determined by direct recording of evoked potentials and electrical stimulation. J. Neurosurg. 51, 476–506 (1979).

    Article  CAS  PubMed  Google Scholar 

  90. McCarthy, G., Allison, T. & Spencer, D. D. Localization of the face area of human sensorimotor cortex by intracranial recording of somatosensory evoked potentials. J. Neurosurg. 79, 874–884 (1993).

    Article  CAS  PubMed  Google Scholar 

  91. Holsheimer, J. et al. The role of intra-operative motor evoked potentials in the optimization of chronic cortical stimulation for the treatment of neuropathic pain. Clin. Neurophysiol. 118, 2287–2296 (2007).

    Article  PubMed  Google Scholar 

  92. Bezard, E. et al. Cortical stimulation and epileptic seizure: a study of the potential risk in primates. Neurosurgery 45, 364–350 (1999).

    Article  Google Scholar 

  93. Maertens de Noordhout, A. et al. Intraoperative localisation of the primary motor cortex using single electrical stimuli. J. Neurol. Neurosurg. Psychiatry 60, 442–444 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Karl, A., Birbaumer, N., Lutzenberger, W., Cohen, L. G. & Flor, H. Reorganization of motor and somatosensory cortex in upper extremity amputees with phantom limb pain. J. Neurosci. 21, 3609–3618 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Coulter, J. D., Maunz, R. A. & Willis, W. D. Effects of stimulation of sensorimotor cortex on primate spinothalamic neurons. Brain Res. 64, 351–356 (1974).

    Article  Google Scholar 

  96. Ranck, L. B. Jr. Which elements are excited in electrical stimulation of mammalian central nervous system: a review. Brain Res. 98, 417–440 (1975).

    Article  PubMed  Google Scholar 

  97. Amassian, V. E., Stewart, M., Quirk, G. J. & Rosenthal, J. L. Physiological basis of motor effects of a transient stimulus to cerebral cortex. Neurosurgery 20, 74–93 (1987).

    CAS  PubMed  Google Scholar 

  98. Amassian, V. E. & Stewart, M. Motor cortical and other cortical interneuronal networks that generate very high frequency waves. Suppl. Clin. Neurophysiol. 56, 119–142 (2003).

    Article  PubMed  Google Scholar 

  99. Manola, L., Holsheimer, J., Veltink, P. & Buitenweg, J. R. Anodal vs cathodal stimulation of motor cortex: a modeling study. Clin. Neurophysiol. 118, 464–474 (2007).

    Article  PubMed  Google Scholar 

  100. Holsheimer, J., Nguyen, J. P., Lefaucheur, J. P. & Manola, L. Cathodal, anodal or bifocal stimulation of the motor cortex in the management of chronic pain. Acta Neurochir. Suppl. 97, 57–66 (2007).

    Article  CAS  PubMed  Google Scholar 

  101. Lefaucheur, J. P., Holsheimer, J., Goujon, C., Keravel, Y. & Nguyen, J. P. Descending volleys generated by efficacious epidural motor cortex stimulation in patients with chronic neuropathic pain. Exp. Neurol. 223, 609–614 (2010).

    Article  PubMed  Google Scholar 

  102. André-Obadia, N., Mertens, P., Gueguen, A., Peyron, R. & Garcia-Larrea, L. Pain relief by rTMS: differential effect of current flow but no specific action on pain subtypes. Neurology 71, 833–840 (2008).

    Article  CAS  PubMed  Google Scholar 

  103. Villanueva, L. & Fields, H. L. Endogenous central mechanisms of pain modulation, in Progress in Pain Research and Management (eds Villanueva, L. et al.) 223–243 (International Association for the Study of Pain, Seattle, 2004).

    Google Scholar 

  104. Peyron, R., Faillenot, I., Mertens, P., Laurent, B. & Garcia-Larrea, L. Motor cortex stimulation in neuropathic pain. Correlations between analgesic effect and hemodynamic changes in the brain. A PET study. Neuroimage 34, 310–321 (2007).

    Article  PubMed  Google Scholar 

  105. Maarrawi, J. et al. Motor cortex stimulation for pain control induces changes in the endogenous opioid system. Neurology 69, 827–834 (2007).

    Article  CAS  PubMed  Google Scholar 

  106. Garcia-Larrea, L. et al. Functional imaging and neurophysiological assessment of spinal and brain therapeutic modulation in humans. Arch. Med. Res. 31, 248–257 (2000).

    Article  CAS  PubMed  Google Scholar 

  107. Lefaucheur, J. P., Drouot, X., Ménard-Lefaucheur, I., Keravel, Y. & Nguyen, J. P. Motor cortex rTMS restores defective intracortical inhibition in chronic neuropathic pain. Neurology 67, 1568–1574 (2006).

    Article  CAS  PubMed  Google Scholar 

  108. Schwenkreis, P. et al. Cortical disinhibition occurs in chronic neuropathic, but not in chronic nociceptive pain. BMC Neurosci. 11, 73–83 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  109. Lima, M. C. & Fregni, F. Motor cortex stimulation for chronic pain: systematic review and meta-analysis of the literature. Neurology 70, 2329–2337 (2008).

    Article  PubMed  Google Scholar 

  110. Fontaine, D., Hamani, C. & Lozano, A. Efficacy and safety of motor cortex stimulation for chronic neuropathic pain: critical review of the literature. J. Neurosurg. 110, 251–256 (2009).

    Article  PubMed  Google Scholar 

  111. Nguyen, J. P. et al. in Neuromodulation (eds Krames, E. S. et al.) Motor cortex stimulation for the treatment of neuropathic pain, 515–526 (Elsevier Science, Amsterdam, 2009).

    Book  Google Scholar 

  112. Rasche, D., Ruppolt, M., Stippich, C., Unterberg, A. & Tronnier, V. Motor cortex stimulation for long-term relief of chronic neuropathic pain: a 10 year experience. Pain 121, 43–52 (2006).

    Article  PubMed  Google Scholar 

  113. Nguyen, J. P. et al. Treatment of chronic neuropathic pain by motor cortex stimulation: Results of a bicentric controlled crossover trial. Brain Stimul. 1, 89–96 (2008).

    Article  PubMed  Google Scholar 

  114. Velasco, F. et al. Efficacy of motor cortex stimulation in the treatment of neuropathic pain: a randomised double-blind trial. J. Neurosurg. 108, 698–706 (2008).

    Article  PubMed  Google Scholar 

  115. Lefaucheur, J. P. et al. Motor cortex stimulation for the treatment of refractory peripheral neuropathic pain. Brain 132, 1463–1471 (2009).

    Article  PubMed  Google Scholar 

  116. Canavero, S., Bonicalzi, V., Castellano, G., Perozzo, P. & Massa-Micon, B. Painful supernumerary phantom arm following motor cortex stimulation for central poststroke pain. J. Neurosurg. 91, 121–123 (1999).

    Article  CAS  PubMed  Google Scholar 

  117. Melzack, R. The McGill Pain Questionnaire: major properties and scoring methods. Pain 1, 277–299 (1975).

    Article  CAS  PubMed  Google Scholar 

  118. Daut, R. L., Cleeland, C. S. & Flanery, R. C. Development of the Wisconsin Brief Pain Questionnaire to assess pain in cancer and other diseases. Pain 17, 197–210 (1983).

    Article  CAS  PubMed  Google Scholar 

  119. Masters Steedman, S. et al. Chronic-pain medications: equivalence levels and method of quantifying usage. Clin. J. Pain 8, 204–214 (1992).

    Article  CAS  PubMed  Google Scholar 

  120. Brown, J. A. & Pilitsis, J. G. Motor cortex stimulation for central and neuropathic facial pain: a prospective study of 10 patients and observations of enhanced sensory and motor function during stimulation. Neurosurgery 56, 290–297 (2005).

    Article  PubMed  Google Scholar 

  121. Henderson, J. M., Boongird, A., Rosenow, J. M, LaPresto, E. & Rezai, A. R. Recovery of pain control by intensive reprogramming after loss of benefit from motor cortex stimulation for neuropathic pain. Stereotact. Funct. Neurosurg. 82, 207–213 (2004).

    Article  PubMed  Google Scholar 

  122. Bergner, M., Bobbitt, R. A., Carter, W. B. & Gilson, B. S. The sickness impact profile: development and final revision of a health status measure. Med. Care 19, 787–805 (1981).

    Article  CAS  PubMed  Google Scholar 

  123. Drouot, X., Nguyen, J. P., Peschanski, M. & Lefaucheur, J. P. The antalgic efficacy of chronic motor cortex stimulation is related to sensory changes in the painful zone. Brain 125, 1660–1664 (2002).

    Article  PubMed  Google Scholar 

  124. André-Obadia, N. et al. Transcranial magnetic stimulation for pain control: double-blind study of different frequencies against placebo, and correlation with motor cortex stimulation efficacy. Clin.Neurophysiol. 117, 1536–1544 (2006).

    Article  PubMed  Google Scholar 

  125. Lefaucheur, J. P., Ménard-Lefaucheur, I., Goujon, C., Keravel, Y. & Nguyen, J. P. Predictive value of rTMS in the identification of responders to epidural motor cortex stimulation therapy for pain. J. Pain doi: 10.1016/j.jpain.2011.05.004.

Download references

Author information

Authors and Affiliations

Authors

Contributions

J.-P. Nguyen, J. Nizard and J.-P. Lefaucheur researched the data for the article. Y. Keravel provided a substantial contribution to discussions of the content. J.-P. Nguyen, J. Nizard and J.-P. Lefaucheur contributed equally to writing the first draft of the article. J.-P. Lefaucheur reviewed and edited the final version of the manuscript.

Corresponding author

Correspondence to Jean-Paul Nguyen.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nguyen, JP., Nizard, J., Keravel, Y. et al. Invasive brain stimulation for the treatment of neuropathic pain. Nat Rev Neurol 7, 699–709 (2011). https://doi.org/10.1038/nrneurol.2011.138

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrneurol.2011.138

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing