Alpha Omega Alpha Honor Medical Society

2010 Research Abstract

Herpes simplex virus vector-mediated expression of interleukin-10 reduces below-level central neuropathic pain after spinal cord injury

Investigator: Darryl Lau, University of Michigan Medical School

Mentor: David J. Fink, MD, University of Michigan Medical School

Neuroimmune activation in the spinal dorsal horn plays an important role in the pathogenesis of chronic pain after peripheral nerve injury. We wanted to examine the role of neuroimmune activation in below level neuropathic pain after traumatic spinal cord injury (SCI). Right 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 non-replicating herpes simplex virus (HSV)-based gene transfer vector (vIL10). Markers of neuroimmune activation were assessed using immunohistochemistry and Western blot. One 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 to 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. Below 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.

Updated on May 14, 2012.

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