Travis Hughes

Controlling chronic pain in humans is a major unresolved problem.  The creation and maintenance of diverse enhanced pain states involve spinal cord astrocytes and microglia via the release of proinflammatory cytokines.  A powerful suppressor of proinflammatory cytokine production and activity is interleukin-10 (IL-10). Local administration of IL-10 protein into the spinal cerebrospinal fluid space (I.T. injection) effectively treats neuropathic pain, albeit transiently (<24 hr) due to its 2-3 hr half-life. Systemic administration of IL-10 protein is ineffective due to its inability to cross the blood-brain barrier and is perhaps undesirable due to the wide spread suppressive effects of IL-10 on the immune system.  The goal of producing localized long-term expression of IL-10 protein in the central nervous system may be amendable to a gene therapy approach.   

Using a peripheral nerve damage-induced chronic neuropathic pain model (CCI) in rat, we have demonstrated long-term pain resolution (>3 mon) with just two closely spaced I.T. injections of a plasmid encoding rat IL-10.  I hypothesize that elements within the plasmid contribute to the efficacy of this gene therapy and that understanding the mechanism of action of these elements will guide optimization of this therapy.  This is the focus of my research.  Knowledge gained from accomplishing the aims of this proposal will guide optimization of the therapy in rat and human, making successful human clinical trials of neuropathic pain treatment much more probable.