Deep brain stimulation for chronic pain: intracranial targets, clinical outcomes, and trial design considerations.

For over half a century, neurosurgeons have attempted to treat pain from a diversity of causes using acute and chronic intracranial stimulation. Targets of stimulation have included the sensory thalamus, periventricular and periaqueductal gray, the septum, the internal capsule, the motor cortex, posterior hypothalamus, and more recently, the anterior cingulate cortex. The current work focuses on presenting and evaluating the evidence for the efficacy of these targets in a historical context while also highlighting the major challenges to having a double-blind placebo-controlled clinical trial. Considerations for pain research in general and use of intracranial targets specifically are included.

[1]  Lemlih Ouchchane,et al.  Anatomical location of effective deep brain stimulation electrodes in chronic cluster headache. , 2010, Brain : a journal of neurology.

[2]  J. Stein,et al.  Peri-ventricular grey stimulation versus motor cortex stimulation for post stroke neuropathic pain , 2002, Journal of Clinical Neuroscience.

[3]  G. Broggi,et al.  Deep brain stimulation to relieve drug‐resistant SUNCT , 2005, Annals of neurology.

[4]  R. Kuroda,et al.  Location of a DBS-electrode in lateral thalamus for deafferentation pain. An autopsy case report. , 1991, Acta neurochirurgica. Supplementum.

[5]  B. Lippitz,et al.  Bilateral chronic electrostimulation of ventroposterolateral pallidum: a new therapeutic approach for alleviating all parkinsonian symptoms. , 1994, Neurosurgery.

[6]  A. Benabid,et al.  Combined (thalamotomy and stimulation) stereotactic surgery of the VIM thalamic nucleus for bilateral Parkinson disease. , 1987, Applied neurophysiology.

[7]  J. Gybels,et al.  Deep brain stimulation in the treatment of chronic pain in man: where and why? , 1990, Neurophysiologie Clinique/Clinical Neurophysiology.

[8]  Y. Hosobuchi Subcortical electrical stimulation for control of intractable pain in humans. Report of 122 cases (1970-1984). , 1986, Journal of neurosurgery.

[9]  Y. Katayama,et al.  Thalamic relay nucleus stimulation for relief of intractable pain. Clinical results and β-endorphin immunoreactivity in the cerebrospinal fluid , 1984, Pain.

[10]  R. Plotkin Results in 60 cases of deep brain stimulation for chronic intractable pain. , 1982, Applied neurophysiology.

[11]  Young Rf,et al.  Pain relief by electrical stimulation of the periaqueductal and periventricular gray matter. Evidence for a non-opioid mechanism. , 1987 .

[12]  P. Roldán,et al.  Chronic VPM stimulation for anesthesia dolorosa following trigeminal surgery. , 1982, Applied neurophysiology.

[13]  J. Pascual,et al.  Neuromodulation of the posterolateral hypothalamus for the treatment of chronic refractory cluster headache: Experience in five patients with a modified anatomical target , 2011, Cephalalgia : an international journal of headache.

[14]  J. Schoenen,et al.  Advances and challenges in neurostimulation for headaches , 2012, The Lancet Neurology.

[15]  C. Sem-Jacobsen DEPTH ELECTROGRAPHIC STIMULATION AND TREATMENT OF PATIENTS WITH PARKINSON'S DISEASE INCLUDING NEUROSURGICAL TECHNIQUE , 1965, Acta neurologica Scandinavica. Supplementum.

[16]  F. Ervin,et al.  Behavioral and affective responses to brain stimulation in man. , 1969, Proceedings of the annual meeting of the American Psychopathological Association.

[17]  M. Bushnell,et al.  Analgesic and placebo effects of thalamic stimulation , 2003, Pain.

[18]  T. Aziz,et al.  Thalamic deep brain stimulation for neuropathic pain after amputation or brachial plexus avulsion. , 2013, Neurosurgical focus.

[19]  J. Boëthius,et al.  Percutaneous central gray stimulation for cancer pain. , 1978, Applied neurophysiology.

[20]  E. G. Szekely,et al.  STIMULATION OF FOREL'S FIELD DURING STEREOTAXIC OPERATIONS IN THE HUMAN BRAIN. , 1964, Electroencephalography and clinical neurophysiology.

[21]  G. Deuschl,et al.  Failure of Deep Brain Stimulation of the Posterior Inferior Hypothalamus in Chronic Cluster Headache - Report of Two Cases and Review of the Literature , 2008, Zentralblatt fur Neurochirurgie.

[22]  H. Fields,et al.  Pain after cortical injury relieved by electrical stimulation of the internal capsule. , 1974, Brain : a journal of neurology.

[23]  J. Siegfried Monopolar electrical stimulation of nucleus ventroposteromedialis thalami for postherpetic facial pain. , 1982, Applied neurophysiology.

[24]  J. Ghika,et al.  Subthalamic DBS replaces levodopa in Parkinson’s disease: Two-year follow-up , 2002, Neurology.

[25]  Y. Hosobuchi,et al.  Autopsy analysis of the safety, efficacy and cartography of electrical stimulation of the central gray in humans , 1986, Brain Research.

[26]  Tipu Z. Aziz,et al.  Deep brain stimulation for pain relief: A meta-analysis , 2005, Journal of Clinical Neuroscience.

[27]  A Franzini,et al.  Stereotactic stimulation of posterior hypothalamic gray matter in a patient with intractable cluster headache. , 2001, The New England journal of medicine.

[28]  O. Andy Parafascicular-center median nuclei stimulation for intractable pain and dyskinesia (painful-dyskinesia). , 1980, Applied neurophysiology.

[29]  A. Lang,et al.  Double-blind evaluation of subthalamic nucleus deep brain stimulation in advanced Parkinson's disease , 1998, Neurology.

[30]  A. Benabid,et al.  Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus , 1991, The Lancet.

[31]  T. Yamamoto,et al.  Clinical results and physiological basis of thalamic relay nucleus stimulation for relief of intractable pain with morphine tolerance. , 1982, Applied neurophysiology.

[32]  G. Broggi,et al.  Update on neurosurgical treatment of chronic trigeminal autonomic cephalalgias and atypical facial pain with deep brain stimulation of posterior hypothalamus: results and comments , 2007, Neurological Sciences.

[33]  Y. Katayama,et al.  Thalamic Sensory Relay Nucleus Stimulation for the Treatment of Peripheral Deafferentation Pain , 2006, Stereotactic and Functional Neurosurgery.

[34]  R. Young,et al.  Contrast medium causes the apparent increase in β-endorphin levels in human cerebrospinal fluid following brain stimulation , 1984, Pain.

[35]  R. Young,et al.  Pain relief by electrical stimulation of the periaqueductal and periventricular gray matter. Evidence for a non-opioid mechanism. , 1987, Journal of neurosurgery.

[36]  J. Stein,et al.  Thalamic field potentials in chronic central pain treated by periventricular gray stimulation – a series of eight cases , 2003, Pain.

[37]  Denys Fontaine,et al.  Safety and efficacy of deep brain stimulation in refractory cluster headache: a randomized placebo-controlled double-blind trial followed by a 1-year open extension , 2009, The Journal of Headache and Pain.

[38]  G. Broggi,et al.  Long-term follow-up of bilateral hypothalamic stimulation for intractable cluster headache. , 2004, Brain : a journal of neurology.

[39]  A. Gol Relief of pain by electrical stimulation of the septal area. , 1967, Journal of the neurological sciences.

[40]  J. Schvarcz Long-term results of stimulation of the septal area for relief of neurogenic pain. , 1993, Acta neurochirurgica. Supplementum.

[41]  Y. Katayama,et al.  Deep Brain Stimulation for Relief of Intractable Pain , 1982 .

[42]  Y. Hosobuchi Combined electrical stimulation of the periaqueductal gray matter and sensory thalamus. , 1983, Applied neurophysiology.

[43]  S Namba,et al.  Sensory and motor responses to deep brain stimulation. Correlation with anatomical structures. , 1985, Journal of neurosurgery.

[44]  Morten L Kringelbach,et al.  Deep brain stimulation of the anterior cingulate cortex: targeting the affective component of chronic pain , 2013, Neuroreport.

[45]  J. Volkmann,et al.  Deep brain stimulation of the posterior hypothalamic area in intractable short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT) , 2011, Cephalalgia : an international journal of headache.

[46]  R. Fessler,et al.  Elevated beta-endorphin in cerebrospinal fluid after electrical brain stimulation: artifact of contrast infusion? , 1984, Science.

[47]  I. Garza Hypothalamic deep brain stimulation for cluster headache: experience from a new multicase series , 2009 .

[48]  P. Wall,et al.  Pain mechanisms: a new theory. , 1965, Science.

[49]  T. Aziz,et al.  N‐of‐1 Trials for Assessing the Efficacy of Deep Brain Stimulation in Neuropathic Pain , 2004, Neuromodulation : journal of the International Neuromodulation Society.

[50]  R. Coffey,et al.  Deep brain stimulation for chronic pain: results of two multicenter trials and a structured review. , 2001, Pain medicine.

[51]  Y. Hosobuchi Dorsal Periaqueductal Gray‐Matter Stimulation in Humans , 1987, Pacing and clinical electrophysiology : PACE.

[52]  Y. Katayama,et al.  [Thalamic relay nucleus stimulation for relief of intractable pain. Clinical results and beta-endorphin immunoreactivity in cerebrospinal fluid]. , 1984, No shinkei geka. Neurological surgery.

[53]  H. Akil,et al.  Pain reduction by electrical brain stimulation in man. Part 1: Acute administration in periaqueductal and periventricular sites. , 1977, Journal of neurosurgery.

[54]  M. Leone,et al.  A Review of Hormonal Findings in Cluster Headache. Evidence for Hypothalamic Involvement , 1993, Cephalalgia : an international journal of headache.

[55]  H. Fields,et al.  Stimulation of internal capsule for relief of chronic pain. , 1974, Journal of neurosurgery.

[56]  Y. Katayama,et al.  Deep brain and motor cortex stimulation for post-stroke movement disorders and post-stroke pain. , 2003, Acta neurochirurgica. Supplement.

[57]  Krishna Kumar,et al.  Deep brain stimulation for control of intractable pain in humans, present and future: a ten-year follow-up. , 1990, Neurosurgery.

[58]  G. Deuschl,et al.  Hypothalamic Deep Brain Stimulation for Cluster Headache: Experience From a New Multicase Series , 2008, Cephalalgia : an international journal of headache.

[59]  George C. Cotzias,et al.  Modification of Parkinsonism--chronic treatment with L-dopa. , 1969, The New England journal of medicine.

[60]  A. L. Green,et al.  Pre-operative DTI and probabilisitic tractography in four patients with deep brain stimulation for chronic pain , 2008, Journal of Clinical Neuroscience.

[61]  G. D'andrea,et al.  Drug-resistant cluster headache: long-term evaluation of pain control by posterior hypothalamic deep-brain stimulation. , 2014, World neurosurgery.

[62]  Grant W. Mallory,et al.  The nucleus accumbens as a potential target for central poststroke pain. , 2012, Mayo Clinic proceedings.

[63]  J. Schvarcz Chronic stimulation of the septal area for the relief of intractable pain. , 1985, Applied neurophysiology.

[64]  J. Krauss,et al.  Center Median-Parafascicular Complex and Pain Control , 2004, Stereotactic and Functional Neurosurgery.

[65]  Clement Hamani,et al.  Deep brain stimulation for chronic neuropathic pain: Long-term outcome and the incidence of insertional effect , 2006, Pain.

[66]  P. Rinaldi,et al.  Chronic stimulation of the Kölliker-Fuse nucleus region for relief of intractable pain in humans. , 1992, Journal of neurosurgery.

[67]  Krishna Kumar,et al.  Deep brain stimulation for intractable pain: a 15-year experience. , 1997, Neurosurgery.

[68]  B. Meyerson,et al.  A correlative anatomical and clinical study of pain suppression by deep brain stimulation , 1982, PAIN.

[69]  T. Aziz,et al.  Deep brain stimulation for phantom limb pain , 2005, Journal of Clinical Neuroscience.

[70]  P Davies,et al.  Deep Brain Stimulation for Neuropathic Cephalalgia , 2006, Cephalalgia : an international journal of headache.

[71]  Y. Hosobuchi TRYPTOPHAN REVERSAL OF TOLERANCE TO ANALGESIA INDUCED BY CENTRAL GREY STIMULATION , 1978, The Lancet.

[72]  R M Levy,et al.  Treatment of chronic pain by deep brain stimulation: long term follow-up and review of the literature. , 1988, Neurosurgery.

[73]  P. Derome,et al.  [CHARACTERISTIC ELECTRIC ACTIVITIES OF SOME CEREBRAL STRUCTURES IN MAN]. , 1963, Annales de chirurgie.

[74]  Y Nakamura,et al.  [Problems of long-term levodopa therapy in Parkinson's disease]. , 1997, Nihon rinsho. Japanese journal of clinical medicine.

[75]  J. Schoenen,et al.  Hypothalamic stimulation in chronic cluster headache: a pilot study of efficacy and mode of action. , 2005, Brain : a journal of neurology.

[76]  Dirk Rasche,et al.  Deep brain stimulation for the treatment of various chronic pain syndromes. , 2006, Neurosurgical focus.

[77]  Gerhard Dieckmann,et al.  Initial and long-term results of deep brain stimulation for chronic intractable pain. , 1982, Applied neurophysiology.

[78]  N. Bekhtereva,et al.  [Utilization of multiple electrodes implanted in the subcortical structure of the human brain for the treatment of hyperkinesis]. , 1963, Zhurnal nevropatologii i psikhiatrii imeni S.S. Korsakova.

[79]  Y. Katayama,et al.  Treatment of Thalamic Pain by Chronic Motor Cortex Stimulation , 1991, Pacing and clinical electrophysiology : PACE.

[80]  J. Burgunder,et al.  Deep brain stimulation of the centre median-parafascicular complex in patients with movement disorders , 2002, Journal of neurology, neurosurgery, and psychiatry.

[81]  A. Benabid,et al.  Electrical stimulation of the subthalamic nucleus in advanced Parkinson's disease. , 1998, The New England journal of medicine.

[82]  K. Takakura,et al.  Posterior Occipital Approach in Deep Brain Stimulation for Both Pain and Involuntary Movement , 1998, Stereotactic and Functional Neurosurgery.

[83]  N. Barbaro,et al.  Chronic stimulation of the posterior hypothalamic region for cluster headache: technique and 1-year results in four patients. , 2007, Journal of neurosurgery.

[84]  Hideki Oshima,et al.  Motor Cortex Stimulation for Post-Stroke Pain: Comparison of Spinal Cord and Thalamic Stimulation , 2002, Stereotactic and Functional Neurosurgery.

[85]  R. Hassler,et al.  [Indications and localization of stereotactic brain operations]. , 1954, Der Nervenarzt.

[86]  R. Young,et al.  Electrical stimulation of the brain in treatment of chronic pain. Experience over 5 years. , 1985, Journal of neurosurgery.

[87]  R. Young,et al.  Electrical stimulation of the brain for relief of intractable pain due to cancer , 1986, Cancer.

[88]  B Carder,et al.  Analgesia from Electrical Stimulation in the Brainstem of the Rat , 1971, Science.

[89]  Tipu Z. Aziz,et al.  Deep brain stimulation for the alleviation of post-stroke neuropathic pain , 2006, Pain.

[90]  Y. Hosobuchi,et al.  Chronic thalamic stimulation for the control of facial anesthesia dolorosa. , 1973, Archives of neurology.

[91]  T. Yamamoto,et al.  Deafferentation pain and stimulation of the thalamic sensory relay nucleus: clinical and experimental study. , 1985, Applied neurophysiology.

[92]  James L Olds,et al.  Positive reinforcement produced by electrical stimulation of septal area and other regions of rat brain. , 1954, Journal of comparative and physiological psychology.

[93]  Y. Hosobuchi,et al.  Pain relief by electrical stimulation of the central gray matter in humans and its reversal by naloxone. , 1977, Science.

[94]  K. Kumar,et al.  Deep brain stimulation for alleviating chronic intractable pain. , 1985, Canadian journal of surgery. Journal canadien de chirurgie.

[95]  A. Machado,et al.  Deep brain stimulation of the ventral striatum/anterior limb of the internal capsule in thalamic pain syndrome: study protocol for a pilot randomized controlled trial , 2013, Trials.

[96]  Robert M. Levy,et al.  Treatment of Chronic Pain by Deep Brain Stimulation: Long Term Follow-up and Review of the Literature , 1987 .

[97]  T. Ohmoto,et al.  Electrical stimulation of the posterior limb of the internal capsule for treatment of thalamic pain. , 1983, Applied neurophysiology.

[98]  L. Merienne,et al.  [Intermittent analgesic thalamic stimulation. Preliminary note]. , 1973, Revue neurologique.

[99]  G. Broggi,et al.  Long-Term Chronic Stimulation of Internal Capsule in Poststroke Pain and Spasticity , 2008, Stereotactic and Functional Neurosurgery.

[100]  G. Broggi,et al.  Hypothalamic stimulation for intractable cluster headache: Long-term experience , 2006, Neurology.

[101]  Y. Katayama,et al.  Motor Cortex Stimulation for Phantom Limb Pain: Comprehensive Therapy with Spinal Cord and Thalamic Stimulation , 2002, Stereotactic and Functional Neurosurgery.

[102]  L. Merienne,et al.  [Treatment of certain types of pain with implantable thalamic stimulators]. , 1974, Neuro-Chirurgie.

[103]  Sensory functions of the skin in primates, with special reference to man : proceedings of the international symposium held at the Wenner-Gren Center, Stockholm, January 1976 , 1976 .

[104]  Y. Katayama,et al.  Pain relief following stimulation of the pontomesencephalic parabrachial region in humans: brain sites for nonopiate-mediated pain control. , 1985, Applied neurophysiology.

[105]  P. Ferroli,et al.  Hypothalamic Deep Brain Stimulation for the Treatment of Chronic Cluster Headaches: A Series Report , 2004, Neuromodulation : journal of the International Neuromodulation Society.

[106]  Alexander L Green,et al.  Long-term outcomes of deep brain stimulation for neuropathic pain. , 2013, Neurosurgery.

[107]  Alexander L Green,et al.  Deep Brain Stimulation for Neuropathic Pain , 2006, Neuromodulation : journal of the International Neuromodulation Society.

[108]  J. Siegfried Sensory Thalamic Neurostimulation for Chronic Pain , 1987, Pacing and clinical electrophysiology : PACE.

[109]  P. Ferroli,et al.  Stimulation of the Posterior Hypothalamus for Treatment of Chronic Intractable Cluster Headaches: First Reported Series , 2003 .

[110]  H. Akil,et al.  Pain reduction by electrical brain stimulation in man. Part 2: Chronic self-administration in the periventricular gray matter. , 1977, Journal of neurosurgery.

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

[112]  C. D. Ray,et al.  Deep brain stimulation for severe, chronic pain. , 1980, Acta neurochirurgica. Supplementum.

[113]  J. Schvarcz Chronic self-stimulation of the medial posterior inferior thalamus for the alleviation of deafferentation pain. , 1980, Acta neurochirurgica. Supplementum.

[114]  Y. Hosobuchi,et al.  Chronic thalamic and internal capsule stimulation for the control of central pain Surg. Neurol., 4 (1975) 91–92 , 1976, Pain.

[115]  H. Akil,et al.  Monoaminergic mechanisms of stimulation-produced analgesia , 1975, Brain Research.

[116]  Pantaleo Romanelli,et al.  Patient-Controlled Deep Brain Stimulation Can Overcome Analgesic Tolerance , 2004, Stereotactic and Functional Neurosurgery.

[117]  M I Hariz,et al.  Thalamic stereotaxis for chronic pain: ablative lesion or stimulation? , 1995, Stereotactic and functional neurosurgery.

[118]  F. Bloom,et al.  Stimulation of human periaqueductal gray for pain relief increases immunoreactive beta-endorphin in ventricular fluid. , 1979, Science.

[119]  E. Valenstein,et al.  Attenuation of Aversive Properties of Peripheral Shock by Hypothalamic Stimulation , 1965, Science.

[120]  W. B. Woodhurst,et al.  Thalamic stimulation for neuropathic pain. , 1980, Journal of neurosurgery.

[121]  D. V. Reynolds,et al.  Surgery in the Rat during Electrical Analgesia Induced by Focal Brain Stimulation , 1969, Science.

[122]  Johnn E. Adams,et al.  Naloxone reversal of analgesia produced by brain stimulation in the human , 1976, Pain.

[123]  I. Cooper,et al.  Anterior chorodial artery ligation for involuntary movements. , 1953, Science.