• Darryl Lau, Steven E Harte, Thomas J Morrow, Shiyong Wang, Marina Mata, and David J Fink.
• Department of Neurology, University of Michigan, Ann Arbor, MI, USA.
• Neurorehabil Neural Repair. 2012 Sep 1;26(7):889-97.

BackgroundNeuroimmune activation in the spinal dorsal horn plays an important role in the pathogenesis of chronic pain after peripheral nerve injury.ObjectiveThe aim of this study was to examine the role of neuroimmune activation in below-level neuropathic pain after traumatic spinal cord injury (SCI).MethodsRight hemilateral SCI was created in male Sprague-Dawley rats by controlled blunt impact through a T12 laminectomy. Pain-related behaviors were assessed using both evoked reflex responses and an operant conflict-avoidance test. Neuroimmune activation was blocked by the anti-inflammatory cytokine interleukin-10 (IL-10) delivered by a nonreplicating herpes simplex virus (HSV)-based gene transfer vector (vIL10). Markers of neuroimmune activation were assessed using immunohistochemistry and Western blot.ResultsOne week after SCI, injured animals demonstrated mechanical allodynia, thermal hyperalgesia, and mechanical hyperalgesia in the hind limbs below the level of injury. Animals inoculated with vIL10 had a statistically significant reduction in all of these measures compared to injured rats or injured rats inoculated with control vector. Conflict-avoidance behavior of injured rats inoculated with vIL10 was consistent with significantly reduced pain compared with injured rats injected with control vector. These behavioral results correlated with a significant decrease in spinal tumor necrosis factor α (mTNFα) expression assessed by Western blot and astrocyte activation assessed by glial fibrillary acidic protein immunohistochemistry.ConclusionBelow-level pain after SCI is characterized by neuroimmune activation (increase mTNFα and astrocyte activation). Blunting of the neuroimmune response by HSV-mediated delivery of IL-10 reduced pain-related behaviors, and may represent a potential novel therapeutic agent.

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