530. Spinal Interleukin-10 (IL-10) Gene Therapy Using Viral and Non-Viral Vectors Controls Inflammatory- and Chronic Constriction Injury-Induced Pain States in Rats

Abstract

Spinal cord glia, via proinflammatory cytokines (interleukin-1, tumor necrosis factor, & interleukin-6), critically mediate the creation/maintenance of pathological pain such as sciatic inflammatory neuropathy (SIN) & chronic constriction injury (CCI). The anti-inflammatory cytokine, IL-10, suppresses proinflammatory cytokine production & function. We have used a variety of gene therapy approaches to examine the efficacy of IL-10 in rat models of neuropathic pain. Behavior was assessed before & after induction of various pain models. Adenoviral vectors expressing the IL-10 gene block &/or reverse exaggerated pain (mechanical allodynia [von Frey test] & thermal hyperalgesia [Hargreaves test]) produced by intrathecal (IT) lumbosacral spinal (LS) delivery of gp120, SIN, & CCI. IT LS delivery of AAV2 encoding IL-10 (AAV2-IL-10) was able to block SIN allodynia [amp] reverse CCI allodynia [amp] thermal hyperalgesia. However, the effects of viral IL-10 delivery systems resulted in reversals in the pain state of short duration. An IL-10-encoding non-viral plasmid vector (NVV) was also introduced IT in the CCI model. In contrast to the viral vectors, this approach resulted in long-lasting reversals of the pain state. Ongoing experiments will assess additional effects of NVV-driven IL-10 protein expression, including the identification of transfected tissue(s). These results suggest that NVV-based IL-10 gene therapy may be a potent addition to the treatments available to neuropathic pain patients.