Highlight from PAIN (Volume 159, Issue 7, July 2018)
How Central is Central Poststroke Pain? The Role of Afferent Input in Poststroke Neuropathic Pain: A Prospective, Open-Label Pilot Study
Simon Haroutounian, Andria L. Ford, Karen Frey, Lone Nikolajsen, Nanna B. Finnerup, Alicia Neiner, Evan D. Kharasch, Pall Karlsson, Michael M. Bottros
- Division of Clinical and Translational Research, Department of Anesthesiology, Washington University in St. Louis School of Medicine, St. Louis, MO
- Washington University Pain Center, Washington University in St. Louis School of Medicine, St. Louis, MO
- Department of Neurology, Washington University in St. Louis School of Medicine, St. Louis, MO
- Department of Clinical Medicine, Danish Pain Research Center, Aarhus University, Aarhus, Denmark
- Department of Anesthesiology and Intensive Care, Aarhus University Hospital, Aarhus
- Department of Neurology, Aarhus University Hospital, Aarhus, Denmark
- The Center for Clinical Pharmacology, St. Louis College of Pharmacy, Washington University in St. Louis, MO
The leading types of poststroke pain are headache, shoulder pain, spasticity, and central poststroke pain (CPSP). CPSP is a neuropathic pain disorder caused by a stroke-related lesion affecting the central somatosensory pathways and accounts for about 25% of poststroke pain cases. CPSP often manifests as a hemipain contralateral to the hemisphere affected by stroke but may also be restricted to a part of the contralateral upper or lower extremity (or both). CPSP is among the most treatment-resistant chronic pain conditions, with the majority of clinical trials failing to show large effect sizes in relieving pain with drugs that otherwise have reasonable effectiveness in other neuropathic pain conditions.
This study’s investigators hypothesized that a stroke-related lesion leads to sensitization of somatosensory CNS neurons in a manner that generates action potentials in response to (previously subthreshold) peripheral sensory input. The hypotheses were tested in a prospective, open-label pilot study by performing peripheral nerve blocks in the painful distribution in a cohort of individuals meeting the criteria for chronic CPSP. If a regional nerve block of the painful extremity in CPSP failed to abolish ongoing pain, this would suggest a central pain-generating mechanism. Inversely, alleviation of the pain by a peripheral nerve block could indicate that CPSP is a consequence of maladaptive change, resulting in sensitization of central nervous system (CNS) neurons to peripheral afferent input.
In this study of 8 subjects with CPSP, the blockade of afferent sensory input from the painful extremity by the means of peripheral regional anesthesia completely abolished pain in all patients at some point within 30 minutes and in 7 of 8 patients at the time of primary outcome assessment (30 minutes after the block). Evoked thermal and mechanical hypersensitivity was abolished in all patients at that time. The success of the blocks was determined by ultrasound verification of perineural local anesthetic distribution.
These results provide evidence that the afferent sensory input has an important role in maintaining pain in patients with CPSP. This supports the hypothesis that after stroke, CPSP may be experienced because of a sensitization of CNS neurons to afferent input rather than autonomous ectopic CNS activity. Emerging preclinical evidence suggests that CNS injury also may cause hyperexcitability of primary afferent neurons; this is an exciting alternative hypothesis that necessitates clinical validation. These findings require further mechanistic investigation into both the central and the peripheral contributors to pain. It would be important to determine the key CNS areas that functionally respond to the blockade of afferent sensory input in CPSP (e.g., by performing functional brain imaging) and how a change in brain activity contributes to analgesia.
Future research should focus on investigating whether neuromodulation of the peripheral nerves, dorsal root ganglia, or the spinal cord, by modifying rather than blocking the afferent input, may have a role in CPSP. This approach may open new therapeutic horizons to target central neuropathic pain syndromes.