EcoHIV and neuropathic pain

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PROJECT SUMMARY/ABSTRACT Chronic pain is a major health condition in people living with Human Immunodeficiency Virus-1 (PLWH) despite the use of combined antiretroviral therapy (ART). Unlike other human immunodeficiency virus (HIV) areas of research (e.g., HIV-associated neurocognitive disorder, vaccine), chronic pain is an understudied area of research despite the prevalence of pain in PLWH, lack of effective analgesic therapy, and incomplete understanding of mechanisms. The development of therapeutic strategies and a better understanding of HIV- related neuropathic pain mechanisms have been hampered by the lack of a suitable animal model that mimics chronic neuropathic pain in PLWH. The current small animal model for HIV-related neuropathic pain consists of the acute administration of a single HIV viral protein, such as glycoprotein 120 (gp120). This model has served to determine the pain response to this viral protein and its mechanism of action. However, in addition to gp120, other HIV viral proteins, HIV-1 transactivator of transcription (Tat), and Viral protein R (Vpr) can produce pain. Therefore, a single HIV protein is unlikely to be the only contributor to HIV-neuropathic pain and mimics the HIV chronic condition where there is a continuous presence of HIV and a simultaneous presence of viral proteins. The proposed studies will test the hypothesis that EcoHIV-infected mice develop a neuropathic pain-like condition with behavioral and pathological changes that mimic PLWH with chronic neuropathic pain. A multidisciplinary approach of behavior, pharmacology, molecular biology, biochemistry, and histopathology will test this hypothesis. Aim 1. We will perform comprehensive studies to characterize neuropathic pain in EcoHIV- infected mice. We will use a battery of behavioral assessments of sensory and spontaneous/ongoing pain. Analyzing markers clinically used for the diagnosis of HIV-associated peripheral neuropathy (e.g., decrease in intraepidermal nerve fiber density) will serve to validate the EcoHIV-associated neuropathic pain model. We will also analyze neuroinflammation, a key player in the induction and maintenance of chronic pain. The proposed studies will have a significant impact on the fields of HIV and pain by providing a small animal model to study HIV-related neuropathic pain, which has been lacking. Characterization of the EcoHIV-related neuropathic pain model will advance current research on pain in the context of HIV by laying the groundwork for urgently and critically needed studies.