Skip to main content
Log in

Neuropathic Pain and Deep Brain Stimulation

  • Review
  • Published:
Neurotherapeutics

Abstract

Deep brain stimulation (DBS) is a neurosurgical intervention the efficacy, safety, and utility of which are established in the treatment of Parkinson’s disease. For the treatment of chronic, neuropathic pain refractory to medical therapies, many prospective case series have been reported, but few have published findings from patients treated with current standards of neuroimaging and stimulator technology over the last decade . We summarize the history, science, selection, assessment, surgery, programming, and personal clinical experience of DBS of the ventral posterior thalamus, periventricular/periaqueductal gray matter, and latterly rostral anterior cingulate cortex (Cg24) in 113 patients treated at 2 centers (John Radcliffe, Oxford, UK, and Hospital de São João, Porto, Portugal) over 13 years. Several experienced centers continue DBS for chronic pain, with success in selected patients, in particular those with pain after amputation, brachial plexus injury, stroke, and cephalalgias including anesthesia dolorosa. Other successes include pain after multiple sclerosis and spine injury. Somatotopic coverage during awake surgery is important in our technique, with cingulate DBS under general anesthesia considered for whole or hemibody pain, or after unsuccessful DBS of other targets. Findings discussed from neuroimaging modalities, invasive neurophysiological insights from local field potential recording, and autonomic assessments may translate into improved patient selection and enhanced efficacy, encouraging larger clinical trials.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Laitinen LV. Surgical treatment, past and present, in Parkinson's disease. Acta Neurol Scand Suppl 1972;51:43–58.

    CAS  PubMed  Google Scholar 

  2. Pereira EA, Aziz TZ. Surgical insights into Parkinson's disease. J R Soc Med 2006;99:238–44.

    PubMed Central  PubMed  Google Scholar 

  3. Ashburn MA, Staats PS. Management of chronic pain. Lancet 1999;353:1865–9.

    CAS  PubMed  Google Scholar 

  4. Gureje O, Von Korff M, Simon GE, Gater R. Persistent pain and well-being: a World Health Organization Study in Primary Care. JAMA 1998;280:147–151.

    CAS  PubMed  Google Scholar 

  5. Jensen TS, Baron R, Haanpaa M, et al. A new definition of neuropathic pain. Pain 2011;152:2204–2205.

    PubMed  Google Scholar 

  6. Torrance N, Smith BH, Bennett MI, Lee AJ. The epidemiology of chronic pain of predominantly neuropathic origin. Results from a general population survey. J Pain 2006;7:281–289.

    PubMed  Google Scholar 

  7. Bouhassira D, Lanteri-Minet M, Attal N, Laurent B, Touboul C. Prevalence of chronic pain with neuropathic characteristics in the general population. Pain 2008;136:380–387.

    PubMed  Google Scholar 

  8. Melzack R, Wall PD. Pain mechanisms: a new theory. Science 1965;150:971–979.

    CAS  PubMed  Google Scholar 

  9. Sweet WH, Wepsic JG. Treatment of chronic pain by stimulation of fibers of primary afferent neuron. Trans Am Neurol Assoc 1968;93:103–107.

    CAS  PubMed  Google Scholar 

  10. Shealy CN, Mortimer JT, Reswick JB. Electrical inhibition of pain by stimulation of the dorsal columns: preliminary clinical report. Anesth Analg 1967;46:489–491.

    CAS  PubMed  Google Scholar 

  11. Mullett K. Electrical brain stimulation for the control of chronic pain. Med Instrum 1978;12:88–91.

    CAS  PubMed  Google Scholar 

  12. Mullett K. State of the art in neurostimulation. Pacing Clin Electrophysiol 1987;10:162–175.

    CAS  PubMed  Google Scholar 

  13. Mayer DJ, Wolfle TL, Akil H, Carder B, Liebeskind JC. Analgesia from electrical stimulation in the brainstem of the rat. Science 1971;174:1351–1354.

    CAS  PubMed  Google Scholar 

  14. Reynolds DV. Surgery in the rat during electrical analgesia induced by focal brain stimulation. Science 1969;164:444–445.

    CAS  PubMed  Google Scholar 

  15. Richardson DE, Akil H. Long term results of periventricular gray self-stimulation. Neurosurgery 1977;1:199–202.

    CAS  PubMed  Google Scholar 

  16. Richardson DE, Akil H. Pain reduction by electrical brain stimulation in man. Part 1: Acute administration in periaqueductal and periventricular sites. J Neurosurg 1977;47:178–183.

    CAS  PubMed  Google Scholar 

  17. Richardson DE, Akil H. Pain reduction by electrical brain stimulation in man. Part 2: Chronic self-administration in the periventricular gray matter. J Neurosurg 1977;47:184–194.

    CAS  PubMed  Google Scholar 

  18. Hosobuchi Y, Adams JE, Linchitz R. Pain relief by electrical stimulation of the central gray matter in humans and its reversal by naloxone. Science 1977;197:183–186.

    CAS  PubMed  Google Scholar 

  19. White JC, Sweet WH. Pain and the neurosurgeon. Charles C Thoms, Springfield, IL, 1969.

    Google Scholar 

  20. Ervin FR, Brown CE, Mark VH. Striatal influence on facial pain. Confin Neurol 1966;27:75–90.

    CAS  PubMed  Google Scholar 

  21. Mark VH, Ervin FR. Role of Thalamotomy in treatment of chronic severe pain. Postgrad Med 1965;37:563–571.

    CAS  PubMed  Google Scholar 

  22. Mark VH, Ervin FR, Hackett TP. Clinical aspects of stereotactic thalamotomy in the human. Part I. The treatment of chronic severe pain. Arch Neurol 1960;3:351–367.

    CAS  PubMed  Google Scholar 

  23. Hosobuchi Y, Adams JE, Rutkin B. Chronic thalamic stimulation for the control of facial anesthesia dolorosa. Arch Neurol 1973;29:158–161.

    CAS  PubMed  Google Scholar 

  24. Mazars G, Merienne L, Cioloca C. [Treatment of certain types of pain with implantable thalamic stimulators]. Neurochirurgie 1974;20:117–124 [in French].

    CAS  PubMed  Google Scholar 

  25. Mazars G, Merienne L, Ciolocca C. [Intermittent analgesic thalamic stimulation. Preliminary note]. Rev Neurol (Paris) 1973;128:273–279 [in French]

    CAS  Google Scholar 

  26. Mazars GJ. Intermittent stimulation of nucleus ventralis posterolateralis for intractable pain. Surg Neurol 1975;4:93–95.

    CAS  PubMed  Google Scholar 

  27. Mazars G, Roge R, Mazars Y. [Results of the stimulation of the spinothalamic fasciculus and their bearing on the physiopathology of pain.]. Rev Prat 1960;103:136–138 [in French].

    CAS  PubMed  Google Scholar 

  28. Adams JE, Hosobuchi Y, Fields HL. Stimulation of internal capsule for relief of chronic pain. J Neurosurg 1974;41:740–744.

    CAS  PubMed  Google Scholar 

  29. Fields HL, Adams JE. Pain after cortical injury relieved by electrical stimulation of the internal capsule. Brain 1974;97:169–178.

    CAS  PubMed  Google Scholar 

  30. Hosobuchi Y, Adams JE, Rutkin B. Chronic thalamic and internal capsule stimulation for the control of central pain. Surg Neurol 1975;4:91–92.

    CAS  PubMed  Google Scholar 

  31. Ray CD, Burton CV. Deep brain stimulation for severe, chronic pain. Acta Neurochir Suppl (Wien) 1980;30:289–293.

    CAS  Google Scholar 

  32. Thoden U, Doerr M, Dieckmann G, Krainick JU. Medial thalamic permanent electrodes for pain control in man: an electrophysiological and clinical study. Electroencephalogr Clin Neurophysiol 1979;47:582–591.

    CAS  PubMed  Google Scholar 

  33. Boivie J, Meyerson BA. A correlative anatomical and clinical study of pain suppression by deep brain stimulation. Pain 1982;13:113–126.

    CAS  PubMed  Google Scholar 

  34. Andy OJ. Parafascicular-center median nuclei stimulation for intractable pain and dyskinesia (painful-dyskinesia). Appl Neurophysiol 1980;43:133–144.

    CAS  PubMed  Google Scholar 

  35. Spooner J, Yu H, Kao C, Sillay K, Konrad P. Neuromodulation of the cingulum for neuropathic pain after spinal cord injury. Case report. J Neurosurg 2007;107:169–172.

    PubMed  Google Scholar 

  36. Foltz EL, White LE, Jr. Pain “relief” by frontal cingulumotomy. J Neurosurg 1962;19:89–100.

    CAS  PubMed  Google Scholar 

  37. Cosgrove GR, Rauch SL. Stereotactic cingulotomy. Neurosurg Clin N Am 2003;14:225–235.

    PubMed  Google Scholar 

  38. Viswanathan A, Harsh V, Pereira EA, Aziz TZ. Cingulotomy for medically refractory cancer pain. Neurosurg Focus 2013;35:E1.

    PubMed  Google Scholar 

  39. Coffey RJ. Deep brain stimulation for chronic pain: results of two multicenter trials and a structured review. Pain Med 2001;2:183–192.

    CAS  PubMed  Google Scholar 

  40. Long DM. The current status of electrical stimulation of the nervous system for the relief of chronic pain. Surg Neurol 1998;49:142–144.

    CAS  PubMed  Google Scholar 

  41. Long DM. Conquering pain. Neurosurgery 2000;46:257–259.

    CAS  PubMed  Google Scholar 

  42. Yamamoto T, Katayama Y, Obuchi T, et al. Thalamic sensory relay nucleus stimulation for the treatment of peripheral deafferentation pain. Stereotact Funct Neurosurg 2006;84:180–183.

    PubMed  Google Scholar 

  43. Hamani C, Schwalb JM, Rezai AR, Dostrovsky JO, Davis KD, Lozano AM. Deep brain stimulation for chronic neuropathic pain: Long-term outcome and the incidence of insertional effect. Pain 2006;125:188–196.

    PubMed  Google Scholar 

  44. Marchand S, Kupers RC, Bushnell MC, Duncan GH. Analgesic and placebo effects of thalamic stimulation. Pain 2003;105:481–488.

    PubMed  Google Scholar 

  45. Rasche D, Rinaldi PC, Young RF, Tronnier VM. Deep brain stimulation for the treatment of various chronic pain syndromes. Neurosurg Focus 2006;21:E8.

    PubMed  Google Scholar 

  46. Levy RM. Deep brain stimulation for the treatment of intractable pain. Neurosurg Clin N Am 2003;14:389–399.

    PubMed  Google Scholar 

  47. Green AL, Owen SL, Davies P, Moir L, Aziz TZ. Deep brain stimulation for neuropathic cephalalgia. Cephalalgia 2006;26:561–567.

    CAS  PubMed  Google Scholar 

  48. Owen SL, Green AL, Stein JF, Aziz TZ. Deep brain stimulation for the alleviation of post-stroke neuropathic pain. Pain 2006;120:202–206.

    PubMed  Google Scholar 

  49. Boccard SG, Pereira EA, Moir L, Aziz TZ, Green AL. Long-term outcomes of deep brain stimulation for neuropathic pain. Neurosurgery 2013;72:221–231.

    PubMed  Google Scholar 

  50. Pereira EA, Boccard SG, Linhares P, et al. Thalamic deep brain stimulation relieves neuropathic pain after amputation or brachial plexus avulsion. Neurosurg Focus 2013;35:1–11.

    CAS  Google Scholar 

  51. Taylor RS. Spinal cord stimulation in complex regional pain syndrome and refractory neuropathic back and leg pain/failed back surgery syndrome: results of a systematic review and meta-analysis. J Pain Symptom Manage 2006;31(4 Suppl.):S13–19.

    PubMed  Google Scholar 

  52. Nguyen JP, Nizard J, Keravel Y, Lefaucheur JP. Invasive brain stimulation for the treatment of neuropathic pain. Nat Rev 2011;7:699–709.

    CAS  Google Scholar 

  53. Kumar K, Taylor RS, Jacques L, et al. 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. Neurosurgery 2008;63:762–770.

    PubMed  Google Scholar 

  54. Kemler MA, de Vet HC, Barendse GA, van den Wildenberg FA, van Kleef M. Effect of spinal cord stimulation for chronic complex regional pain syndrome Type I: five-year final follow-up of patients in a randomized controlled trial. J Neurosurg 2008;108:292–298.

    PubMed  Google Scholar 

  55. Manca A, Kumar K, Taylor RS, et al. Quality of life, resource consumption and costs of spinal cord stimulation versus conventional medical management in neuropathic pain patients with failed back surgery syndrome (PROCESS trial). Eur J Pain 2008;12:1047–1058.

    PubMed  Google Scholar 

  56. Nandi D, Smith H, Owen S, Joint C, Stein J, Aziz T. Peri-ventricular grey stimulation versus motor cortex stimulation for post stroke neuropathic pain. J Clin Neurosci 2002;9:557–561.

    PubMed  Google Scholar 

  57. 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 2001;77:183–186.

    CAS  PubMed  Google Scholar 

  58. Katayama Y, Yamamoto T, Kobayashi K, Kasai M, Oshima H, Fukaya C. Motor cortex stimulation for phantom limb pain: comprehensive therapy with spinal cord and thalamic stimulation. Stereotact Funct Neurosurg 2001;77:159–162.

    CAS  PubMed  Google Scholar 

  59. Coffey RJ, Lozano AM. Neurostimulation for chronic noncancer pain: an evaluation of the clinical evidence and recommendations for future trial designs. J Neurosurg 2006;105:175–189.

    PubMed  Google Scholar 

  60. Levy R, Deer TR, Henderson J. Intracranial neurostimulation for pain control: a review. Pain Physician 2011;13:157–165.

    Google Scholar 

  61. Anderson WS, Ohara S, Lawson HC, Treede RD, Lenz FA. Chapter 21 Plasticity of pain-related neuronal activity in the human thalamus. Prog Brain Res 2006;157:353–364.

    CAS  PubMed  Google Scholar 

  62. Melzack R, Coderre TJ, Katz J, Vaccarino AL. Central neuroplasticity and pathological pain. Ann N Y Acad Sci 2001;933:157–174.

    CAS  PubMed  Google Scholar 

  63. Coderre TJ, Katz J, Vaccarino AL, Melzack R. Contribution of central neuroplasticity to pathological pain: review of clinical and experimental evidence. Pain 1993;52:259–285.

    CAS  PubMed  Google Scholar 

  64. Schweinhardt P, Lee M, Tracey I. Imaging pain in patients: is it meaningful? Curr Opin Neurol 2006;19:392–400.

    PubMed  Google Scholar 

  65. Stern J, Jeanmonod D, Sarnthein J. Persistent EEG overactivation in the cortical pain matrix of neurogenic pain patients. Neuroimage 2006;31:721–731.

    PubMed  Google Scholar 

  66. Apkarian AV, Bushnell MC, Treede RD, Zubieta JK. Human brain mechanisms of pain perception and regulation in health and disease. Eur J Pain 2005;9:463–484.

    PubMed  Google Scholar 

  67. Saint-Cyr JA, Trepanier LL. Neuropsychologic assessment of patients for movement disorder surgery. Mov Disord 2000;15:771–783.

    CAS  PubMed  Google Scholar 

  68. Voon V, Kubu C, Krack P, Houeto JL, Troster AI. Deep brain stimulation: neuropsychological and neuropsychiatric issues. Mov Disord 2006;21(Suppl. 14):S305–327.

    PubMed  Google Scholar 

  69. Lang AE, Houeto JL, Krack P, et al. Deep brain stimulation: preoperative issues. Mov Disord 2006;21(Suppl. 14):S171–196.

    PubMed  Google Scholar 

  70. Shulman R, Turnbull IM, Diewold P. Psychiatric aspects of thalamic stimulation for neuropathic pain. Pain 1982;13:127–135.

    CAS  PubMed  Google Scholar 

  71. Pereira EA, Green AL, Aziz TZ. Deep brain stimulation for pain. Handb Clin Neurol 2013;116:277–294.

    PubMed  Google Scholar 

  72. Bittar RG, Otero S, Carter H, Aziz TZ. Deep brain stimulation for phantom limb pain. J Clin Neurosci 2005;12:399–404.

    PubMed  Google Scholar 

  73. Owen SLF, Green AL, Nandi D, Bittar RG, Wang S, Aziz TZ. Deep brain stimulation for neuropathic pain. Neuromodulation 2006;9:100–106.

    PubMed  Google Scholar 

  74. Ramachandran VS, Rogers-Ramachandran D. Phantom limbs and neural plasticity. Arch Neurol 2000;57:317–320.

    CAS  PubMed  Google Scholar 

  75. Janig W, Baron R. Complex regional pain syndrome is a disease of the central nervous system. Clin Auton Res 2002;12:150–164.

    PubMed  Google Scholar 

  76. Janig W, Baron R. Complex regional pain syndrome: mystery explained? Lancet Neurol 2003;2:687–697.

    PubMed  Google Scholar 

  77. Janig W, Baron R. Is CRPS I a neuropathic pain syndrome? Pain 2006;120:227–229.

    PubMed  Google Scholar 

  78. Ramachandran VS. Plasticity and functional recovery in neurology. Clin Med 2005;5:368–373.

    CAS  PubMed  Google Scholar 

  79. Pereira EA, Moir L, McIntyre C, Green AL, Aziz TZ. Deep brain stimulation for central post-stroke pain – relating outcomes and stimulation parameters in 21 patients. Acta Neurochir 2008;150:968.

    Google Scholar 

  80. Green AL, Nandi D, Armstrong G, Carter H, Aziz T. Post-herpetic trigeminal neuralgia treated with deep brain stimulation. J Clin Neurosci 2003;10:512–54.

    CAS  PubMed  Google Scholar 

  81. Owen SL, Green AL, Nandi DD, Bittar RG, Wang S, Aziz TZ. Deep brain stimulation for neuropathic pain. Acta Neurochir Suppl 2007;97:111–116.

  82. Boccard SG, Pereira EA, Moir L, et al. Deep brain stimulation of the anterior cingulate cortex: targeting the affective component of chronic pain. Neuroreport 2014;25:83–88.

  83. Lenz FA, Dostrovsky JO, Tasker RR, Yamashiro K, Kwan HC, Murphy JT. Single-unit analysis of the human ventral thalamic nuclear group: somatosensory responses. J Neurophysiol 1988;59:299–316.

    CAS  PubMed  Google Scholar 

  84. Bittar RG, Nandi D, Carter H, Aziz TZ. Somatotopic organization of the human periventricular gray matter. J Clin Neurosci 2005;12:240–241.

    PubMed  Google Scholar 

  85. Pereira EA, Wang S, Owen SL, Aziz TZ, Green AL. Human periventricular grey somatosensory evoked potentials suggest rostrocaudally inverted somatotopy. Stereotact Funct Neurosurg 2013;91:290–297.

    PubMed  Google Scholar 

  86. Romanelli P, Esposito V. The functional anatomy of neuropathic pain. Neurosurg Clin N Am 2004;15:257–268.

    PubMed  Google Scholar 

  87. Peyron R, Laurent B, Garcia-Larrea L. Functional imaging of brain responses to pain. A review and meta-analysis (2000). Neurophysiol Clin 2000;30:263–288.

    CAS  PubMed  Google Scholar 

  88. Tracey I. Nociceptive processing in the human brain. Curr Opin Neurobiol 2005;15:478–487.

    CAS  PubMed  Google Scholar 

  89. Sewards TV, Sewards MA. The medial pain system: neural representations of the motivational aspect of pain. Brain Res Bull 2002;59:163–180.

    PubMed  Google Scholar 

  90. Gauriau C, Bernard JF. Pain pathways and parabrachial circuits in the rat. Exp Physiol 2002;87:251–258.

    PubMed  Google Scholar 

  91. Willis WD, Westlund KN. Neuroanatomy of the pain system and of the pathways that modulate pain. J Clin Neurophysiol 1997;14:2–31.

  92. Behbehani MM. Functional characteristics of the midbrain periaqueductal gray. Prog Neurobiol 1995;46:575–605.

    CAS  PubMed  Google Scholar 

  93. Craig AD. Pain mechanisms: labeled lines versus convergence in central processing. Annu Rev Neurosci 2003;26:1–30.

    CAS  PubMed  Google Scholar 

  94. Kupers R, Kehlet H. Brain imaging of clinical pain states: a critical review and strategies for future studies. Lancet Neurol 2006;5:1033–1044.

    PubMed  Google Scholar 

  95. Wu D, Wang S, Stein JF, Aziz TZ, Green AL. Reciprocal interactions between the human thalamus and periaqueductal gray may be important for pain perception. Exp Brain Res 2014;232:527–534.

    PubMed  Google Scholar 

  96. Yamashiro K, Tomiyama N, Terada Y, Samura H, Mukawa J, Tasker RR. Neurons with spontaneous high-frequency discharges in the central nervous system and chronic pain. Acta Neurochir Suppl 2003;87:153–155.

    CAS  PubMed  Google Scholar 

  97. Duncan GH, Bushnell MC, Marchand S. Deep brain stimulation: a review of basic research and clinical studies. Pain 1991;45:49–59.

    CAS  PubMed  Google Scholar 

  98. Gybels JM, Sweet WH. Neurosurgical treatment of persistent pain. Physiological and pathological mechanisms of human pain. In: Gildenberg PL (ed.) Pain and headache. 1st ed. Karger, Basel, 1989;81–92

  99. Weigel R, Krauss JK. Center median-parafascicular complex and pain control. Review from a neurosurgical perspective. Stereotact Funct Neurosurg 2004;82:115–126.

    PubMed  Google Scholar 

  100. Tronnier VM. Deep brain stimulation. In: Simpson BA (ed.) Pain research and clinical management, v. 15. Elsevier, Amsterdam, 2003, pp. 211–236.

    Google Scholar 

  101. Young RF, Rinaldi PC. Brain stimulation. In: North RB, Levy RM (eds) Neurosurgical management of pain. Springer-Verlag, New York, 1997, pp. 283–301.

    Google Scholar 

  102. Brown P. Oscillatory nature of human basal ganglia activity: Relationship to the pathophysiology of Parkinson's disease. Mov Disord 2003;18:357–363.

    PubMed  Google Scholar 

  103. Engel AK, Moll CK, Fried I, Ojemann GA. Invasive recordings from the human brain: clinical insights and beyond. Nat Rev Neurosci 2005;6:35–47.

    CAS  PubMed  Google Scholar 

  104. Hutchison WD, Dostrovsky JO, Walters JR, et al. Neuronal oscillations in the basal ganglia and movement disorders: evidence from whole animal and human recordings. J Neurosci 2004;24:9240–9243.

    CAS  PubMed  Google Scholar 

  105. Nandi D, Aziz TZ. Deep brain stimulation in the management of neuropathic pain and multiple sclerosis tremor. J Clin Neurophysiol 2004;21:31–39.

    PubMed  Google Scholar 

  106. Bittar RG, Burn SC, Bain PG, et al. Deep brain stimulation for movement disorders and pain. J Clin Neurosci 2005;12:457–463.

    PubMed  Google Scholar 

  107. 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 2003;101:97–107.

    PubMed  Google Scholar 

  108. Nandi D, Liu X, Joint C, Stein J, Aziz T. Thalamic field potentials during deep brain stimulation of periventricular gray in chronic pain. Pain 2002;97:47–51.

    PubMed  Google Scholar 

  109. Xie K, Wang S, Aziz TZ, Stein JF, Liu X. The physiologically modulated electrode potentials at the depth electrode-brain interface in humans. Neurosci Lett 2006;402:238–243.

    CAS  PubMed  Google Scholar 

  110. Green AL, Wang S, Stein JF, et al. Neural signatures in patients with neuropathic pain. Neurology 2009;72:569–571.

    CAS  PubMed Central  PubMed  Google Scholar 

  111. Kringelbach ML, Jenkinson N, Green AL, et al. Deep brain stimulation for chronic pain investigated with magnetoencephalography. Neuroreport 2007;18:223–228.

    PubMed  Google Scholar 

  112. Ray NJ, Jenkinson N, Kringelbach ML, et al. Abnormal thalamocortical dynamics may be altered by deep brain stimulation: using magnetoencephalography to study phantom limb pain. J Clin Neurosci 2009;16:32–36.

    CAS  PubMed  Google Scholar 

  113. Pereira EA, Green AL, Bradley KM, et al. Regional cerebral perfusion differences between periventricular grey, thalamic and dual target deep brain stimulation for chronic neuropathic pain. Stereotact Funct Neurosurg 2007;85:175–183.

    PubMed  Google Scholar 

  114. Rossi F, Maione S, Berrino L. Periaqueductal gray area and cardiovascular function. Pharmacol Res 1994;29:27–37.

    CAS  PubMed  Google Scholar 

  115. Bandler R, Keay KA, Floyd N, Price J. Central circuits mediating patterned autonomic activity during active vs. passive emotional coping. Brain Res Bull 2000;53:95–104.

    CAS  PubMed  Google Scholar 

  116. Carrive P. The periaqueductal gray and defensive behavior: functional representation and neuronal organization. Behav Brain Res 1993;58:27–47.

    CAS  PubMed  Google Scholar 

  117. Bandler R, Carrive P, Zhang SP. Integration of somatic and autonomic reactions within the midbrain periaqueductal grey: viscerotopic, somatotopic and functional organization. Prog Brain Res 1991;87:269–305.

    CAS  PubMed  Google Scholar 

  118. Green AL, Wang S, Owen SL, et al. Stimulating the human midbrain to reveal the link between pain and blood pressure. Pain 2006;124:349–359.

    PubMed  Google Scholar 

  119. Green AL, Wang S, Owen SL, et al. Deep brain stimulation can regulate arterial blood pressure in awake humans. Neuroreport 2005;16:1741–1745.

    PubMed  Google Scholar 

  120. Green AL, Wang S, Owen SL, Paterson DJ, Stein JF, Aziz TZ. Controlling the heart via the brain: a potential new therapy for orthostatic hypotension. Neurosurgery 2006;58:1176–1183.

    PubMed  Google Scholar 

  121. Pereira EA, Wang S, Paterson DJ, Stein JF, Aziz TZ, Green AL. Sustained reduction of hypertension by deep brain stimulation. J Clin Neurosci 2010;17:124–127.

    PubMed  Google Scholar 

  122. Pereira EA, Lu G, Wang S, et al. Ventral periaqueductal grey stimulation alters heart rate variability in humans with chronic pain. Exp Neurol 2010;223:574–581.

    PubMed  Google Scholar 

  123. Akil H, Liebeskind JC. Monoaminergic mechanisms of stimulation-produced analgesia. Brain Res 1975;94:279–296.

    CAS  PubMed  Google Scholar 

  124. Akil H, Mayer DJ, Liebeskind JC. Antagonism of stimulation-produced analgesia by naloxone, a narcotic antagonist. Science 1976;191:961–962.

    CAS  PubMed  Google Scholar 

  125. Akil H, Richardson DE, Hughes J, Barchas JD. Enkephalin-like material elevated in ventricular cerebrospinal fluid of pain patients after analgetic focal stimulation. Science 1978;201:463–465.

    CAS  PubMed  Google Scholar 

  126. Hosobuchi Y, Rossier J, Bloom FE, Guillemin R. Stimulation of human periaqueductal gray for pain relief increases immunoreactive beta-endorphin in ventricular fluid. Science 1979;203:279–281.

    CAS  PubMed  Google Scholar 

  127. Dionne RA, Mueller GP, Young RF, et al. Contrast medium causes the apparent increase in beta-endorphin levels in human cerebrospinal fluid following brain stimulation. Pain 1984;20:313–321.

    CAS  PubMed  Google Scholar 

  128. Fessler RG, Brown FD, Rachlin JR, Mullan S, Fang VS. Elevated beta-endorphin in cerebrospinal fluid after electrical brain stimulation: artifact of contrast infusion? Science 1984;224:1017–1019.

    CAS  PubMed  Google Scholar 

  129. Young RF, Chambi VI. Pain relief by electrical stimulation of the periaqueductal and periventricular gray matter. Evidence for a non-opioid mechanism. J Neurosurg 1987;66:364–371.

    CAS  PubMed  Google Scholar 

  130. Meyerson BA. Biochemistry of pain relief with intracerebral stimulation. Few facts and many hypotheses. Acta Neurochir Suppl (Wien) 1980;30:229–237.

    CAS  Google Scholar 

  131. Pereira EA, Wang S, Peachey T, et al. Elevated gamma band power in humans receiving naloxone suggests dorsal periaqueductal and periventricular gray deep brain stimulation produced analgesia is opioid mediated. Exp Neurol 2013;239:248–255.

    CAS  PubMed  Google Scholar 

  132. Blackburn-Munro G. Pain-like behaviours in animals – how human are they? Trends Pharmacol Sci 2004;25:299–305.

    CAS  PubMed  Google Scholar 

  133. Oliveras JL, Besson JM. Stimulation-produced analgesia in animals: behavioural investigations. Prog Brain Res 1988;77:141–157.

    CAS  PubMed  Google Scholar 

  134. Joint C, Nandi D, Parkin S, Gregory R, Aziz T. Hardware-related problems of deep brain stimulation. Mov Disord 2002;17(Suppl. 3):S175–180.

    PubMed  Google Scholar 

  135. McLeod RS, Taylor DW, Cohen Z, Cullen JB. Single-patient randomised clinical trial. Use in determining optimum treatment for patient with inflammation of Kock continent ileostomy reservoir. Lancet 1986;1:726–728.

    CAS  PubMed  Google Scholar 

  136. McQuay H. N of 1 trials. In: Max MB, Laska EM (eds) The design of analgesic Clinical trials. Raven Press, New York, 1990, pp. 174–192.

    Google Scholar 

  137. Pereira EA, Green AL, Nandi D, Aziz TZ. Deep brain stimulation: indications and evidence. Expert Rev Med Devices 2007;4:591–603.

    PubMed  Google Scholar 

  138. Green AL, Shad A, Watson R, Nandi D, Yianni J, Aziz TZ. N-of-1 trials for assessing the efficacy of deep brain stimulation in neuropathic pain. Neuromodulation 2004;7:76–81.

    PubMed  Google Scholar 

  139. Cruccu G, Aziz TZ, Garcia-Larrea L, et al. EFNS guidelines on neurostimulation therapy for neuropathic pain. Eur J Neurol 2007;14:952–970.

    CAS  PubMed  Google Scholar 

  140. NICE. NHS National Institute for Health and Clinical Excellence guideline IPG 382. Deep brain stimulation for chronic pain syndromes (excluding headache). Available at: http://publications.nice.org.uk/deep-brain-stimulation-for-refractory-chronic-pain-syndromes-excluding-headache-ipg382. Accessed 11 May 2014.

  141. Kaplitt MG, Rezai AR, Lozano AM, Tasker RR. Deep brain stimulation for chronic pain. In: Winn HR (ed.) Youmans neurological surgery. 5th ed. Saunders, Philadelphia, PA, 2004, pp. 3118–3131.

    Google Scholar 

  142. Bendok BR, Levy RM, Onibukon A. Deep brain stimulation for the treatment of intractable pain. In: Batjer HH, Loftus CM (eds) Textbook of neurological surgery : principles and practice. Lippincott Williams & Wilkins, Philadelphia, PA, 2003, pp. 2673–2681.

    Google Scholar 

  143. Meyerson BA. Problems and controversies in PVG and sensory thalamic stimulation as treatment for pain. Prog Brain Res 1988;77:175-188.

    CAS  PubMed  Google Scholar 

  144. Adams JE, Hosobuchi Y. Technique and technical problems. Neurosurgery 1977;1:196–199.

    CAS  PubMed  Google Scholar 

  145. Adams JE, Hosobuchi Y, Linchitz R. The present status of implantable intracranial stimulators for pain. Clin Neurosurg 1977;24:347–361.

    CAS  PubMed  Google Scholar 

  146. Burchiel KJ. Deep brain stimulation for chronic pain: the results of two multi-center trials and a structured review. Pain Med 2001;2:177.

    CAS  PubMed  Google Scholar 

  147. Bittar RG, Kar-Purkayastha I, Owen SL, et al. Deep brain stimulation for pain relief: a meta-analysis. J Clin Neurosci 2005;12:515–519.

    PubMed  Google Scholar 

  148. Garonzik I, Samdani A, Ohara S, Lenz FA. Deep brain stimulation for the control of pain. Epilepsy Behav 2001;2(3 Suppl. 3):S55–60.

    Google Scholar 

  149. Gybels J. Thalamic stimulation in neuropathic pain: 27 years later. Acta Neurol Belg 2001;101:65–71.

    CAS  PubMed  Google Scholar 

  150. Gybels J, Erdine S, Maeyaert J, et al. Neuromodulation of pain. A consensus statement prepared in Brussels 16-18 January 1998 by the following task force of the European Federation of IASP Chapters (EFIC). Eur J Pain 1998;2:203–209.

    CAS  PubMed  Google Scholar 

  151. Krauss JK, Pohle T, Weigel R, Burgunder JM. Deep brain stimulation of the centre median-parafascicular complex in patients with movement disorders. J Neurol Neurosurg Psychiatry 2002;72:546–548.

    CAS  PubMed Central  PubMed  Google Scholar 

  152. Raslan AM. Deep brain stimulation for chronic pain: can it help? Pain 2006;120:1–2.

    PubMed  Google Scholar 

  153. Tasker RR, Filho OV. Deep brain stimulation for neuropathic pain. Stereotact Funct Neurosurg 1995;65:122–124.

    CAS  PubMed  Google Scholar 

  154. Wallace BA, Ashkan K, Benabid AL. Deep brain stimulation for the treatment of chronic, intractable pain. Neurosurg Clin N Am 2004;15:343–357.

    PubMed  Google Scholar 

  155. Simpson BA. Spinal cord and brain stimulation. In: Wall PD, Melzack R (eds) Textbook of pain. 4th ed. Churchill Livingstone, Edinburgh, 1999, pp. 1353–1382.

    Google Scholar 

  156. Simpson BA. Spinal cord and brain stimulation. In: McMahon S, Koltzenburg M (eds) Wall and Melzack's textbook of pain. 5th ed. Churchill Livingstone, Edinburgh, 2003.

    Google Scholar 

  157. Siegfried J. Therapeutical neurostimulation—indications reconsidered. Acta Neurochir Suppl (Wien) 1991;52:112–117.

    CAS  Google Scholar 

  158. North RB, Levy RM. Consensus conference on the neurosurgical management of pain. Neurosurgery 1994;34:756–760.

    CAS  PubMed  Google Scholar 

  159. Osenbach R. Neurostimulation for the treatment of intractable facial pain. Pain Med 2006;7(Suppl. 1):S126–S136.

    Google Scholar 

  160. Hosobuchi Y. The current status of analgesic brain stimulation. Acta Neurochir Suppl (Wien) 1980;30:219–227.

    CAS  Google Scholar 

  161. Hosobuchi Y. Current issues regarding subcortical electrical stimulation for pain control in humans. Prog Brain Res 1988;77:189–192.

    CAS  PubMed  Google Scholar 

  162. Stojanovic MP. Stimulation methods for neuropathic pain control. Curr Pain Headache Rep 2001;5:130–137.

    CAS  PubMed  Google Scholar 

  163. Gildenberg PL. History of electrical neuromodulation for chronic pain. Pain Med 2006;7 (Suppl. 1):S7–S13.

    Google Scholar 

  164. Mazars G, Merienne L, Cioloca C. Comparative study of electrical stimulation of posterior thalamic nuclei, periaqueductal gray, and other midline mesencephalic structures in man. In: Bonica JJ, Liebeskind JC, Albe-Fessard DG (eds) Advances in pain research and therapy. Raven Press, New York, 1979, pp. 541–546.

    Google Scholar 

  165. Gybels J. Electrical stimulation of the brain for pain control in human. Verh Dtsch Ges Inn Med 1980;86:1553–1559.

    CAS  PubMed  Google Scholar 

  166. Schvarcz JR. Chronic self-stimulation of the medial posterior inferior thalamus for the alleviation of deafferentation pain. Acta Neurochir Suppl (Wien) 1980;30:295–301.

    CAS  Google Scholar 

  167. Turnbull IM, Shulman R, Woodhurst WB. Thalamic stimulation for neuropathic pain. J Neurosurg 1980;52:486–493.

    CAS  PubMed  Google Scholar 

  168. Dieckmann G, Witzmann A. Initial and long-term results of deep brain stimulation for chronic intractable pain. Appl Neurophysiol 1982;45:167–172.

    CAS  PubMed  Google Scholar 

  169. Plotkin R. Results in 60 cases of deep brain stimulation for chronic intractable pain. Appl Neurophysiol 1982;45:173–178.

    CAS  PubMed  Google Scholar 

  170. Tsubokawa T, Yamamoto T, Katayama Y, Hirayama T, Sibuya H. Thalamic relay nucleus stimulation for relief of intractable pain. Clinical results and beta-endorphin immunoreactivity in the cerebrospinal fluid. Pain 1984;18:115–126.

    CAS  PubMed  Google Scholar 

  171. Tsubokawa T, Yamamoto T, Katayama Y, Moriyasu N. Clinical results and physiological basis of thalamic relay nucleus stimulation for relief of intractable pain with morphine tolerance. Appl Neurophysiol 1982;45:143–155.

    CAS  PubMed  Google Scholar 

  172. Tsubokawa T, Katayama Y, Yamamoto T, Hirayama T. Deafferentation pain and stimulation of the thalamic sensory relay nucleus: clinical and experimental study. Appl Neurophysiol 1985;48:166–171.

    CAS  PubMed  Google Scholar 

  173. Meyerson BA. Electrostimulation procedures: Effects, presumed rationale, and possible mechanisms. Adv Pain Res Ther 1983;5:495–534.

    Google Scholar 

  174. Hosobuchi Y. Chronic brain stimulation for the treatment of intractable pain. Res Clin Stud Headache 1978;5:122–126.

    CAS  PubMed  Google Scholar 

  175. Hosobuchi Y. Dorsal periaqueductal gray-matter stimulation in humans. Pacing Clin Electrophysiol 1987;10:213–216.

    CAS  PubMed  Google Scholar 

  176. Hosobuchi Y. Subcortical electrical stimulation for control of intractable pain in humans. Report of 122 cases (1970–1984). J Neurosurg 1986;64:543–553.

    CAS  PubMed  Google Scholar 

  177. Hosobuchi Y. Combined electrical stimulation of the periaqueductal gray matter and sensory thalamus. Appl Neurophysiol 1983;46:112–115.

    CAS  PubMed  Google Scholar 

  178. Baskin DS, Mehler WR, Hosobuchi Y, Richardson DE, Adams JE, Flitter MA. Autopsy analysis of the safety, efficacy and cartography of electrical stimulation of the central gray in humans. Brain Res 1986;371:231–236.

    CAS  PubMed  Google Scholar 

  179. Levy RM, Lamb S, Adams JE. Treatment of chronic pain by deep brain stimulation: long term follow-up and review of the literature. Neurosurgery 1987;21:885–893.

    CAS  PubMed  Google Scholar 

  180. Siegfried J. Sensory thalamic neurostimulation for chronic pain. Pacing Clin Electrophysiol 1987;10:209–212.

    CAS  PubMed  Google Scholar 

  181. Gybels J, Kupers R. Deep brain stimulation in the treatment of chronic pain in man: where and why? Neurophysiol Clin 1990;20:389–398.

    CAS  PubMed  Google Scholar 

  182. Young RF, Kroening R, Fulton W, Feldman RA, Chambi I. Electrical stimulation of the brain in treatment of chronic pain. Experience over 5 years. J Neurosurg 1985;62:389–396.

    PubMed  Google Scholar 

  183. Young RF, Brechner T. Electrical stimulation of the brain for relief of intractable pain due to cancer. Cancer 1986;57:1266–1272.

    CAS  PubMed  Google Scholar 

  184. Kumar K, Toth C, Nath RK. Deep brain stimulation for intractable pain: a 15-year experience. Neurosurgery 1997;40:736–746.

    CAS  PubMed  Google Scholar 

  185. 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 Neurochir Suppl 2003;87:121–123.

    CAS  PubMed  Google Scholar 

  186. Gybels J, Kupers R, Nuttin B. Therapeutic stereotactic procedures on the thalamus for pain. Acta Neurochir (Wien) 1993;124:19–22.

    CAS  Google Scholar 

  187. Dunckley P, Wise RG, Fairhurst M, et al. A comparison of visceral and somatic pain processing in the human brainstem using functional magnetic resonance imaging. J Neurosci 2005;25:7333–7341.

    CAS  PubMed  Google Scholar 

  188. Chang L. Brain responses to visceral and somatic stimuli in irritable bowel syndrome: a central nervous system disorder? Gastroenterol Clin North Am 2005;34:271–279.

    PubMed  Google Scholar 

  189. Owen SL, Heath J, Kringelbach M, et al. Pre-operative DTI and probabilisitic tractography in four patients with deep brain stimulation for chronic pain. J Clin Neurosci 2008;15:801–805.

    CAS  PubMed  Google Scholar 

  190. Sillery E, Bittar RG, Robson MD, et al. Connectivity of the human periventricular-periaqueductal gray region. J Neurosurg 2005;103:1030–1034.

    PubMed  Google Scholar 

  191. Johansen-Berg H, Behrens TE. Just pretty pictures? What diffusion tractography can add in clinical neuroscience. Curr Opin Neurol 2006;19:379–385.

    PubMed Central  PubMed  Google Scholar 

  192. Mohseni HR, Kringelbach ML, Probert Smith P, et al. Application of a null-beamformer to source localisation in MEG data of deep brain stimulation. Conf Proc IEEE Eng Med Biol Soc 2010;2010:4120–4123.

    PubMed  Google Scholar 

  193. Makela JP, Forss N, Jaaskelainen J, Kirveskari E, Korvenoja A, Paetau R. Magnetoencephalography in neurosurgery. Neurosurgery 2006;59:493–511.

    PubMed  Google Scholar 

  194. Kamano S. Author's experience of lateral medullary infarction—thermal perception and muscle allodynia. Pain 2003;104:49–53.

    PubMed  Google Scholar 

  195. Romanelli P, Heit G. Patient-controlled deep brain stimulation can overcome analgesic tolerance. Stereotact Funct Neurosurg 2004;82:77–79.

    PubMed  Google Scholar 

  196. Hariz MI, Shamsgovara P, Johansson F, Hariz G, Fodstad H. Tolerance and tremor rebound following long-term chronic thalamic stimulation for Parkinsonian and essential tremor. Stereotact Funct Neurosurg 1999;72:208–218.

    CAS  PubMed  Google Scholar 

  197. Boccard SG, Pereira EA, Moir L, et al. Targeting the affective component of chronic pain: a case series of deep brain stimulation of the anterior cingulate cortex. Neurosurgery 2014;74(6):628–637.

  198. Pereira EA, Paranathala M, Hyam JA, Green AL, Aziz TZ. Anterior cingulotomy improves malignant mesothelioma pain and dyspnoea. Br J Neurosurg 2013. doi:10.3109/02688697.2013.857006.

Download references

Acknowledgments

This work was supported by the UK Medical Research Council, Norman Collisson Foundation, Charles Wolfson Charitable Trust, and Oxford NIHR Biomedical Research Centre.

Required Author Forms

Disclosure forms provided by the authors are available with the online version of this article.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Erlick A. C. Pereira.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(PDF 1224 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pereira, E.A.C., Aziz, T.Z. Neuropathic Pain and Deep Brain Stimulation. Neurotherapeutics 11, 496–507 (2014). https://doi.org/10.1007/s13311-014-0278-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13311-014-0278-x

Key Words

Navigation