Modulating the pain network—neurostimulation for central poststroke pain

Key Points

  • 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.

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Figure 1: Lesion sites associated with central poststroke pain.
Figure 2: Neurostimulation targets in the CNS.


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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.

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All authors contributed equally to researching data for the article, discussion of the content, writing the article and reviewing and/or editing of the manuscript before submission.

Correspondence to Youichi Saitoh.

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Competing interests

K.H. and Y.S. have received support from Teijin Pharma. B.S. declares no competing interests.

Supplementary information

Supplementary Table 1

Stimulation targets in studies of deep brain stimulation (DOCX 21 kb)

Supplementary Table 2

Details of experimental design in studies of high-frequency repetitive transcranial magnetic stimulation of the primary motor cortex (DOCX 25 kb)

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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

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