Central poststroke pain (CPSP) is an under-recognized and severe complication of stroke, and remains extremely difficult to treat by conventional pharmacological means
Pathophysiologically, CPSP might be best understood as a network reorganization disorder that leads to a maladaptive central state in which selective disruption of spinothalamic sensory pathways is a key feature
The network reorganization hypothesis offers insight into nonpharmacological treatments for CPSP—such as neurostimulation—that target specific network nodes
Of the invasive neuromodulatory strategies, electrical motor cortex stimulation is the most efficient, but the benefits must be carefully balanced against the risks of invasive treatments
Noninvasive repetitive transcranial magnetic stimulation of the motor cortex is currently the preferred treatment approach, but must be applied repeatedly to maintain its effect
A greater understanding of the pathophysiology of CPSP, together with technological innovation, could lead to safer, more-practical and more-efficient treatments
Central poststroke pain (CPSP) is one of the most under-recognized consequences of stroke, occurring in up to 10% of patients, and is also one of the most difficult to treat. The condition characteristically develops after selective lesions to the spinothalamic system, most often to the ventral posterior thalamus. Here, we suggest that CPSP is best characterized as a disorder of brain network reorganization, and that this characterization offers insight into the inadequacy of most current pharmacological treatments. Accordingly, we review the progress in identification of nonpharmacological treatments, which could ultimately lead to mechanism-based therapeutics. Of the invasive neurostimulation treatments available, electrical motor cortex stimulation seems to be superior to deep brain stimulation of the thalamus or brainstem, but enthusiasm for clinical use of the procedure is limited by its invasiveness. The current preference is for noninvasive transcranial magnetic stimulation, which, though effective, requires repeated application, causing logistical difficulties. Although CPSP is often severe and remains difficult to treat, future characterization of the precise underlying neurophysiological mechanisms, together with technological innovation, should allow new treatments to evolve.
Subscribe to Journal
Get full journal access for 1 year
only $17.75 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Dejerine, J. & Roussy, G. Le syndrome thalamique. Rev. Neurol. (Paris) 14, 521–532 (1906).
Kim, J. S. Post-stroke pain. Expert Rev. Neurother. 9, 711–721 (2009).
Klit, H., Finnerup, N. B. & Jensen, T. S. Central post-stroke pain: clinical characteristics, pathophysiology, and management. Lancet Neurol. 8, 857–868 (2009).
IASP Taxonomy. International Association for the Study of Pain [online], (2014).
Kim, J. S. Pharmacological management of central post-stroke pain: a practical guide. CNS Drugs 28, 787–797 (2014).
Andersen, G., Vestergaard, K., Ingeman-Nielsen, M. & Jensen, T. S. Incidence of central post-stroke pain. Pain 61, 187–193 (1995).
Bowsher, D. Stroke and central poststroke pain in an elderly population. J. Pain 2, 258–261 (2001).
Weimar, C., Kloke, M., Schlott, M., Katsarava, Z. & Diener, H. C. Central poststroke pain in a consecutive cohort of stroke patients. Cerebrovasc. Dis. 14, 261–263 (2002).
Widar, M., Samuelsson, L., Karlsson-Tivenius, S. & Ahlström, G. Long-term pain conditions after a stroke. J. Rehabil. Med. 34, 165–170 (2002).
Kong, K. H., Woon, V. C. & Yang, S. Y. Prevalence of chronic pain and its impact on health-related quality of life in stroke survivors. Arch. Phys. Med. Rehabil. 85, 35–40 (2004).
Jönsson, A. C., Lindgren, I., Hallström, B., Norrving, B. & Lindgren, A. Prevalence and intensity of pain after stroke: a population based study focusing on patients' perspectives. J. Neurol. Neurosurg. Psychiatry 77, 590–595 (2006).
Lundström, E., Smits, A., Terent, A. & Borg, J. Risk factors for stroke-related pain 1 year after first-ever stroke. Eur. J. Neurol. 16, 188–193 (2009).
Klit, H., Finnerup, N. B., Andersen, G. & Jensen, T. S. Central poststroke pain: a population-based study. Pain 152, 818–824 (2011).
Raffaeli, W., Minella, C. E., Magnani, F. & Sarti, D. Population-based study of central post-stroke pain in Rimini district, Italy. J. Pain Res. 6, 705–711 (2013).
Harno, H. et al. Central poststroke pain in young ischemic stroke survivors in the Helsinki Young Stroke Registry. Neurology 83, 1147–1154 (2014).
O'Donnell, M. J. et al. Chronic pain syndromes after ischemic stroke: PRoFESS trial. Stroke 44, 1238–1243 (2013).
Boivie, J., Leijon, G. & Johansson, I. Central post-stroke pain—a study of the mechanisms through analyses of the sensory abnormalities. Pain 37, 173–185 (1989).
Holmgren, H., Leijon, G., Boivie, J., Johansson, I. & Ilievska, L. Central post-stroke pain—somatosensory evoked potentials in relation to location of the lesion and sensory signs. Pain 40, 43–52 (1990).
Vestergaard, K. et al. Sensory abnormalities in consecutive, unselected patients with central post-stroke pain. Pain 61, 177–186 (1995).
Leijon, G., Boivie, J. & Johansson, I. Central post-stroke pain—neurological symptoms and pain characteristics. Pain 36, 13–25 (1989).
Bowsher, D., Leijon, G. & Thuomas, K. A. Central poststroke pain: correlation of MRI with clinical pain characteristics and sensory abnormalities. Neurology 51, 1352–1358 (1998).
MacGowan, D. J. et al. Central poststroke pain and Wallenberg's lateral medullary infarction: frequency, character, and determinants in 63 patients. Neurology 49, 120–125 (1997).
Lampl, C., Yazdi, K. & Roper, C. Amitriptyline in the prophylaxis of central poststroke pain. Preliminary results of 39 patients in a placebo-controlled, long-term study. Stroke 33, 3030–3032 (2002).
Lenz, F. A. et al. Thermal and pain sensations evoked by microstimulation in the area of human ventrocaudal nucleus. J. Neurophysiol. 70, 200–212 (1993).
Kumar, B., Kalita, J., Kumar, G. & Misra, U. K. Central poststroke pain: a review of pathophysiology and treatment. Anesth. Analg. 108, 1645–1657 (2009).
Kumar, G. & Soni, C. R. Central post-stroke pain: current evidence. J. Neurol. Sci. 284, 10–17 (2009).
Flaster, M., Meresh, E., Rao, M. & Biller, J. Central poststroke pain: current diagnosis and treatment. Top. Stroke Rehabil. 20, 116–123 (2013).
Krause, T. et al. Thalamic sensory strokes with and without pain: differences in lesion patterns in the ventral posterior thalamus. J. Neurol. Neurosurg. Psychiatry 83, 776–784 (2012).
Sprenger, T. et al. Assessing the risk of central post-stroke pain of thalamic origin by lesion mapping. Brain 135, 2536–2545 (2012).
Craig, A. D., Bushnell, M. C., Zhang, E. T. & Blomqvist, A. A thalamic nucleus specific for pain and temperature sensation. Nature 372, 770–773 (1994).
Kim, J. S. Central post-stroke pain or paresthesia in lenticulocapsular hemorrhages. Neurology 61, 679–682 (2003).
Garcia-Larrea, L. et al. Operculo-insular pain (parasylvian pain): a distinct central pain syndrome. Brain 133, 2528–2539 (2010).
Kim, J. S. Patterns of sensory abnormality in cortical stroke: evidence for a dichotomized sensory system. Neurology 68, 174–180 (2007).
Treede, R. D. et al. Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neurology 70, 1630–1635 (2008).
Bowsher, D. Central pain: clinical and physiological characteristics. J. Neurol. Neurosurg. Psychiatry 61, 62–69 (1996).
Melzack, R. & Wall, P. D. Pain mechanisms: a new theory. Science 150, 971–979 (1965).
Vogt, B. A. & Sikes, R. W. The medial pain system, cingulate cortex, and parallel processing of nociceptive information. Prog. Brain Res. 122, 223–235 (2000).
Apkarian, A. V., Baliki, M. N. & Geha, P. Y. Towards a theory of chronic pain. Prog. Neurobiol. 87, 81–97 (2009).
Mano, H. & Seymour, B. Pain: a distributed brain information network? PLoS Biol. 13, e1002037 (2015).
Greenspan, J. D., Ohara, S., Sarlani, E. & Lenz, F. A. Allodynia in patients with post-stroke central pain (CPSP) studied by statistical quantitative sensory testing within individuals. Pain 109, 357–366 (2004).
Lenz, F. A., Kwan, H. C., Dostrovsky, J. O. & Tasker, R. R. Characteristics of the bursting pattern of action potentials that occurs in the thalamus of patients with central pain. Brain Res. 496, 357–360 (1989).
Craig, A. D., Reiman, E. M., Evans, A. & Bushnell, M. C. Functional imaging of an illusion of pain. Nature 384, 258–260 (1996).
Craig, A. D. in Central Neuropathic Pain: Focus on Poststroke Pain (eds Henry, J. L. et al.) 81–99 (IASP Press, 2007).
Craig, A. D. & Bushnell, M. C. The thermal grill illusion: unmasking the burn of cold pain. Science 265, 252–255 (1994).
Kern, D., Pelle-Lancien, E., Luce, V. & Bouhassira, D. Pharmacological dissection of the paradoxical pain induced by a thermal grill. Pain 135, 291–299 (2008).
Craig, A. D. Can the basis for central neuropathic pain be identified by using a thermal grill? Pain 135, 215–216 (2008).
Kim, J. H., Greenspan, J. D., Coghill, R. C., Ohara, S. & Lenz, F. A. Lesions limited to the human thalamic principal somatosensory nucleus (ventral caudal) are associated with loss of cold sensations and central pain. J. Neurosci. 27, 4995–5004 (2007).
Garcia-Larrea, L. et al. Laser-evoked potential abnormalities in central pain patients: the influence of spontaneous and provoked pain. Brain 125, 2766–2781 (2002).
Radhakrishnan, V. et al. A comparison of the burst activity of lateral thalamic neurons in chronic pain and non-pain patients. Pain 80, 567–575 (1999).
Wang, G. & Thompson, S. M. Maladaptive homeostatic plasticity in a rodent model of central pain syndrome: thalamic hyperexcitability after spinothalamic tract lesions. J. Neurosci. 28, 11959–11969 (2008).
Ducreux, D., Attal, N., Parker, F. & Bouhassira, D. Mechanisms of central neuropathic pain: a combined psychophysical and fMRI study in syringomyelia. Brain 129, 963–976 (2006).
Casey, K. L. et al. Psychophysical and cerebral responses to heat stimulation in patients with central pain, painless central sensory loss, and in healthy persons. Pain 153, 331–341 (2012).
Willoch, F. et al. Central poststroke pain and reduced opioid receptor binding within pain processing circuitries: a [11C]diprenorphine PET study. Pain 108, 213–220 (2004).
Krause, T. et al. The cortical signature of central poststroke pain: gray matter decreases in somatosensory, insular, and prefrontal cortices. Cereb. Cortex http://dx.doi.org/10.1093/cercor/bhu177.
Soria, E. D. & Fine, E. J. Disappearance of thalamic pain after parietal subcortical stroke. Pain 44, 285–288 (1991).
Helmchen, C., Lindig, M., Petersen, D. & Tronnier, V. Disappearance of central thalamic pain syndrome after contralateral parietal lobe lesion: implications for therapeutic brain stimulation. Pain 98, 325–330 (2002).
Baliki, M. N., Mansour, A. R., Baria, A. T. & Apkarian, A. V. Functional reorganization of the default mode network across chronic pain conditions. PLoS ONE 9, e106133 (2014).
Farmer, M. A., Baliki, M. N. & Apkarian, A. V. A dynamic network perspective of chronic pain. Neurosci. Lett. 520, 197–203 (2012).
Frese, A., Husstedt, I. W., Ringelstein, E. B. & Evers, S. Pharmacologic treatment of central post-stroke pain. Clin. J. Pain 22, 252–260 (2006).
Leijon, G. & Boivie, J. Central post-stroke pain—a controlled trial of amitriptyline and carbamazepine. Pain 36, 27–36 (1989).
Vestergaard, K., Andersen, G., Gottrup, H., Kristensen, B. T. & Jensen, T. S. Lamotrigine for central poststroke pain: a randomized controlled trial. Neurology 56, 184–190 (2001).
Attal, N. et al. Intravenous lidocaine in central pain: a double-blind, placebo-controlled, psychophysical study. Neurology 54, 564–574 (2000).
Canavero, S. & Bonicalzi, V. Intravenous subhypnotic propofol in central pain: a double-blind, placebo-controlled, crossover study. Clin. Neuropharmacol. 27, 182–186 (2004).
Vranken, J. H. et al. Pregabalin in patients with central neuropathic pain: a randomized, double-blind, placebo-controlled trial of a flexible-dose regimen. Pain 136, 150–157 (2008).
Kim, J. S. et al. Safety and efficacy of pregabalin in patients with central post-stroke pain. Pain 152, 1018–1023 (2011).
Jungehulsing, G. J. et al. Levetiracetam in patients with central neuropathic post-stroke pain—a randomized, double-blind, placebo-controlled trial. Eur. J. Neurol. 20, 331–337 (2013).
Mazars, G. J. Intermittent stimulation of nucleus ventralis posterolateralis for intractable pain. Surg. Neurol. 4, 93–95 (1975).
Hosobuchi, Y., Adams, J. E. & Rutkin, B. Chronic thalamic stimulation for the control of facial anesthesia dolorosa. Arch. Neurol. 29, 158–161 (1973).
Adams, J. E., Hosobuchi, Y. & Fields, H. L. Stimulation of internal capsule for relief of chronic pain. J. Neurosurg. 41, 740–744 (1974).
Richardson, D. E. & Akil, H. Long term results of periventricular gray self-stimulation. Neurosurgery 1, 199–202 (1977).
Turnbull, I. M., Shulman, R. & Woodhurst, W. B. Thalamic stimulation for neuropathic pain. J. Neurosurg. 52, 486–493 (1980).
Hosobuchi, Y. Subcortical electrical stimulation for control of intractable pain in humans. Report of 122 cases (1970–1984). J. Neurosurg. 64, 543–553 (1986).
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).
Kumar, K., Toth, C. & Nath, R. K. Deep brain stimulation for intractable pain: a 15-year experience. Neurosurgery 40, 736–746 (1997).
Katayama, Y. et al. Motor cortex stimulation for post-stroke pain: comparison of spinal cord and thalamic stimulation. Stereotact. Funct. Neurosurg. 77, 183–186 (2001).
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).
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).
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).
Boccard, S. G. et al. Targeting the affective component of chronic pain: a case series of deep brain stimulation of the anterior cingulate cortex. Neurosurgery 74, 628–635 (2014).
Cruccu, G. et al. EFNS guidelines on neurostimulation therapy for neuropathic pain. Eur. J. Neurol. 14, 952–970 (2007).
Nguyen, J. P., Nizard, J., Keravel, Y. & Lefaucheur, J. P. Invasive brain stimulation for the treatment of neuropathic pain. Nat. Rev. Neurol. 7, 699–709 (2011).
Bittar, R. G. et al. Deep brain stimulation for pain relief: a meta-analysis. J. Clin. Neurosci. 12, 515–519 (2005).
Dworkin, R. H. et al. Interventional management of neuropathic pain: NeuPSIG recommendations. Pain 154, 2249–2261 (2013).
Levy, R., Deer, T. R. & Henderson, J. Intracranial neurostimulation for pain control: a review. Pain Physician 13, 157–165 (2010).
Tsubokawa, T., Katayama, Y., Yamamoto, T., Hirayama, T. & Koyama, S. Chronic motor cortex stimulation for the treatment of central pain. Acta Neurochir. Suppl. (Wien) 52, 137–139 (1991).
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).
Tsubokawa, T., Katayama, Y., Yamamoto, T., Hirayama, T. & Koyama, S. Treatment of thalamic pain by chronic motor cortex stimulation. Pacing Clin. Electrophysiol. 14, 131–134 (1991).
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).
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).
Nandi, D. et al. Peri-ventricular grey stimulation versus motor cortex stimulation for post stroke neuropathic pain. J. Clin. Neurosci. 9, 557–561 (2002).
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).
Gharabaghi, A. et al. Volumetric image guidance for motor cortex stimulation: integration of three-dimensional cortical anatomy and functional imaging. Neurosurgery 57, 114–120 (2005).
Nuti, C. et al. Motor cortex stimulation for refractory neuropathic pain: four year outcome and predictors of efficacy. Pain 118, 43–52 (2005).
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 (2 Suppl.), 344–359 (2005).
Rasche, D., Ruppolt, M., Stippich, C., Unterberg, A. & Tronnier, V. M. Motor cortex stimulation for long-term relief of chronic neuropathic pain: a 10 year experience. Pain 121, 43–52 (2006).
Hosomi, K. et al. Electrical stimulation of primary motor cortex within the central sulcus for intractable neuropathic pain. Clin. Neurophysiol. 119, 993–1001 (2008).
Velasco, F. et al. Efficacy of motor cortex stimulation in the treatment of neuropathic pain: a randomized double-blind trial. J. Neurosurg. 108, 698–706 (2008).
Lefaucheur, J. P., Keravel, Y. & Nguyen, J. P. Treatment of poststroke pain by epidural motor cortex stimulation with a new octopolar lead. Neurosurgery 68 (1 Suppl. Operative), 180–187 (2011).
Tanei, T. et al. Efficacy of motor cortex stimulation for intractable central neuropathic pain: comparison of stimulation parameters between post-stroke pain and other central pain. Neurol. Med. Chir. (Tokyo) 51, 8–14 (2011).
Sachs, A. J., Babu, H., Su, Y. F., Miller, K. J. & Henderson, J. M. Lack of efficacy of motor cortex stimulation for the treatment of neuropathic pain in 14 patients. Neuromodulation 17, 303–310 (2014).
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).
Saitoh, Y. & Yoshimine, T. Stimulation of primary motor cortex for intractable deafferentation pain. Acta Neurochir. Suppl. 97, 51–56 (2007).
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 12, 1102–1111 (2011).
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).
André-Obadia, N. et al. Is life better after motor cortex stimulation for pain control? Results at long-term and their prediction by preoperative rTMS. Pain Physician 17, 53–62 (2014).
Migita, K., Uozumi, T., Arita, K. & Monden, S. Transcranial magnetic coil stimulation of motor cortex in patients with central pain. Neurosurgery 36, 1037–1039 (1995).
de Oliveira, R. A. et al. Repetitive transcranial magnetic stimulation of the left premotor/dorsolateral prefrontal cortex does not have analgesic effect on central post-stroke pain. J. Pain 15, 1271–1281 (2014).
Lefaucheur, J. P., Drouot, X., Keravel, Y. & Nguyen, J. P. Pain relief induced by repetitive transcranial magnetic stimulation of precentral cortex. Neuroreport 12, 2963–2965 (2001).
Lefaucheur, J. P., Drouot, X. & Nguyen, J. P. Interventional neurophysiology for pain control: duration of pain relief following repetitive transcranial magnetic stimulation of the motor cortex. Neurophysiol. Clin. 31, 247–252 (2001).
Lefaucheur, J. P. et al. Neurogenic pain relief by repetitive transcranial magnetic cortical stimulation depends on the origin and the site of pain. J. Neurol. Neurosurg. Psychiatry 75, 612–616 (2004).
Khedr, E. M. et al. Longlasting antalgic effects of daily sessions of repetitive transcranial magnetic stimulation in central and peripheral neuropathic pain. J. Neurol. Neurosurg. Psychiatry 76, 833–838 (2005).
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).
Lefaucheur, J. P., Drouot, X., Menard-Lefaucheur, I., Keravel, Y. & Nguyen, J. P. Motor cortex rTMS restores defective intracortical inhibition in chronic neuropathic pain. Neurology 67, 1568–1574 (2006).
Saitoh, Y. et al. Reduction of intractable deafferentation pain due to spinal cord or peripheral lesion by high-frequency repetitive transcranial magnetic stimulation of the primary motor cortex. J. Neurosurg. 107, 555–559 (2007).
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).
Lefaucheur, J. P., Drouot, X., Ménard-Lefaucheur, I., Keravel, Y. & Nguyen, J. P. Motor cortex rTMS in chronic neuropathic pain: pain relief is associated with thermal sensory perception improvement. J. Neurol. Neurosurg. Psychiatry 79, 1044–1049 (2008).
André-Obadia, N., Magnin, M. & Garcia-Larrea, L. On the importance of placebo timing in rTMS studies for pain relief. Pain 152, 1233–1237 (2011).
Hosomi, K. et al. Daily repetitive transcranial magnetic stimulation of primary motor cortex for neuropathic pain: a randomized, multicenter, double-blind, crossover, sham-controlled trial. Pain 154, 1065–1072 (2013).
Goto, T. et al. Diffusion tensor fiber tracking in patients with central post-stroke pain; correlation with efficacy of repetitive transcranial magnetic stimulation. Pain 140, 509–518 (2008).
O'Connell, N. E., Wand, B. M., Marston, L., Spencer, S. & Desouza, L. H. Non-invasive brain stimulation techniques for chronic pain. Cochrane Database of Systematic Reviews, Issue 4. Art No.: CD008208. http://dx.doi.org/10.1002/14651858.CD008208.pub3.
Lefaucheur, J. P. et al. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Clin. Neurophysiol. 125, 2150–2206 (2014).
Leung, A. et al. rTMS for suppressing neuropathic pain: a meta-analysis. J. Pain 10, 1205–1216 (2009).
Lima, M. C. & Fregni, F. Motor cortex stimulation for chronic pain: systematic review and meta-analysis of the literature. Neurology 70, 2329–2337 (2008).
Lefaucheur, J. P. Principles of therapeutic use of transcranial and epidural cortical stimulation. Clin. Neurophysiol. 119, 2179–2184 (2008).
Hosomi, K. et al. Cortical excitability changes after high-frequency repetitive transcranial magnetic stimulation for central poststroke pain. Pain 154, 1352–1357 (2013).
Ohn, S. H. et al. Neural correlates of the antinociceptive effects of repetitive transcranial magnetic stimulation on central pain after stroke. Neurorehabil. Neural Repair 26, 344–352 (2012).
Lefaucheur, J. P. The use of repetitive transcranial magnetic stimulation (rTMS) in chronic neuropathic pain. Neurophysiol. Clin. 36, 117–124 (2006).
Simpson, B. A. Spinal cord stimulation in 60 cases of intractable pain. J. Neurol. Neurosurg. Psychiatry 54, 196–199 (1991).
Aly, M. M. et al. Spinal cord stimulation for central poststroke pain. Neurosurgery 67 (2 Suppl. Operative), ons206–ons212 (2010).
Linderoth, B. Spinal cord stimulation: a brief update on mechanisms of action. Eur. J. Pain. Supp. 3, 89–93 (2009).
Yakhnitsa, V., Linderoth, B. & Meyerson, B. A. Spinal cord stimulation attenuates dorsal horn neuronal hyperexcitability in a rat model of mononeuropathy. Pain 79, 223–233 (1999).
Kishima, H. et al. Modulation of neuronal activity after spinal cord stimulation for neuropathic pain; H215O PET study. Neuroimage 49, 2564–2569 (2010).
Hayashi, M. et al. Outcome after pituitary radiosurgery for thalamic pain syndrome. Int. J. Radiat. Oncol. Biol. Phys. 69, 852–857 (2007).
Bae, S. H., Kim, G. D. & Kim, K. Y. Analgesic effect of transcranial direct current stimulation on central post-stroke pain. Tohoku J. Exp. Med. 234, 189–195 (2014).
Alstott, J., Breakspear, M., Hagmann, P., Cammoun, L. & Sporns, O. Modeling the impact of lesions in the human brain. PLoS Comput. Biol. 5, e1000408 (2009).
Bullmore, E. & Sporns, O. Complex brain networks: graph theoretical analysis of structural and functional systems. Nat. Rev. Neurosci. 10, 186–198 (2009).
Bainton, T., Fox, M., Bowsher, D. & Wells, C. A double-blind trial of naloxone in central post-stroke pain. Pain 48, 159–162 (1992).
Attal, N. et al. Effects of IV morphine in central pain: a randomized placebo-controlled study. Neurology 58, 554–563 (2002).
Vranken, J. H., Dijkgraaf, M. G., Kruis, M. R., van Dasselaar, N. T. & van der Vegt, M. H. Iontophoretic administration of S+-ketamine in patients with intractable central pain: a placebo-controlled trial. Pain 118, 224–231 (2005).
The authors would like to thank Ms Keiko Sano for her assistance in preparing artwork. K.H., B.S. and Y.S. are supported by the Strategic Research Program for Brain Sciences from the Ministry of Education, Culture, Sports, Science and Technology of Japan. B.S. is also funded by the Wellcome Trust (UK) and the National Institute of Information and Communications Technology (Japan). Y.S. is also supported by the Japanese Ministry of Health, Labour and Welfare.
K.H. and Y.S. have received support from Teijin Pharma. B.S. declares no competing interests.
About this article
Cite this article
Hosomi, K., Seymour, B. & Saitoh, Y. Modulating the pain network—neurostimulation for central poststroke pain. Nat Rev Neurol 11, 290–299 (2015) doi:10.1038/nrneurol.2015.58
Deep brain stimulation of the posterior limb of the internal capsule in the treatment of central poststroke neuropathic pain of the lower limb: case series with long-term follow-up and literature review
Journal of Neurosurgery (2019)
Motor cortex stimulation: a systematic literature-based analysis of effectiveness and case series experience
BMC Neurology (2019)
Current Opinion in Supportive and Palliative Care (2019)
The Japanese Journal of Rehabilitation Medicine (2019)