Gene therapy of HIV-neuropathic pain with morphine tolerance

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DESCRIPTION (provided by applicant): Opiate drug abuse and human immunodeficiency virus (HIV) infection/AIDS are two major public health problems. HIV-associated sensory neuropathy (HIV-SN) is the most common neurological complication of HIV infection. The symptoms of HIV-SN are dominated by distal neuropathic pain. Substantial evidence implicates spinal glia activation/products in the pathogenesis of neuropathic pain, and recent data suggests that resident immune cells in the nervous system may represent an important point of intersection between opiate abuse and HIV-SN. In order to investigate the interaction between these two processes (chronic opioid use and painful HIV-SN) we propose a series of experiments to critically test the hypothesis that activation of glia plays a key role in the interaction of chronic morphine treatment with HIV-SN neuropathic pain. In Specific Aim 1 we will define the effects of morphine tolerance and HIV-SN neuropathic pain using behavioral analysis and Western blot, immunohostochemistry and ELISA measures of glial activation. In Specific Aim 2 we will critically test the hypothesis by examining whether inhibition of glial activation/products using herpes simplex virus vector-based gene transfer in the spinal cord reduces pain in morphine tolerant animals with HIV-SN neuropathic pain. This series of behavioral, neurochemical and immunohistochemical studies will provide important new information about the mechanisms by which enhanced glia activation releasing proinflammatory cytokines induces spinal sensitization, and may point towards novel therapeutic approaches to treat that pain in morphine tolerance. These studies will provide preliminary data for future long-term research of the mechanisms and treatment of HIV-related pain. PUBLIC HEALTH RELEVANCE: This proposal will investigate the mechanism of interaction of HIV-neuropathic pain and morphine tolerance. The research may provide a novel approach to treatment of HIV-neuropathic pain with morphine tolerance.