Work

Herpes Simplex Virus Vector–Mediated Expression of Interleukin-10 Reduces Below-Level Central Neuropathic Pain After Spinal Cord Injury

Year: 2012

Type: article

Abstract: BACKGROUND: Neuroimmune activation in the spinal dorsal horn plays an important role in the pathogenesis of chronic pain after peripheral nerve injury. OBJECTIVE: The aim of this study was to examine the role of neuroimmune activation in below-level neuropathic pain after traumatic spinal cord injury (SCI). METHODS: 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 nonreplicating herpes simplex virus (HSV)-based gene transfer vector (vIL10). Markers of neuroimmune activation were assessed using immunohistochemistry and Western blot. RESULTS: 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 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. CONCLUSION: 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.

Source: Neurorehabilitation and neural repair

DOI: 10.1177/1545968312445637

Authors: Darryl Lau, Steven E. Harte, Thomas J. Morrow, Shiyong Wang, Marina Mata, David J. Fink

Institutions: University of Michigan, VA Ann Arbor Healthcare System

Language: English

Topic: Pain Mechanisms and Treatments

Subfield: Physiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke