ABSTRACT Opioid-based analgesics are commonly used for temporal relief of severe pain in HIV-1/AIDS patients. However, recent clinical data show that chronic opioid treatment causes a heightened pain state (hyperalgesia). This debilitating side effect requires escalating dosages of the analgesics in order to be effective, and thus may directly contribute to opioid overdose and epidemics. To prevent this clinically important side effect, it is necessary to understand how chronic use of opioids causes hyperalgesia in HIV patients. In the HIV-1 gp120 mouse model that recapitulates extensive pain-related pathologies of HIV human patients, we simulate morphine exacerbation of gp120-induced pain. The goal of this project is to elucidate the pathogenic mechanism by which morphine potentiates HIV-associated pain. Our prior work reveals that neuroinflammation in the spinal cord dorsal horn (SDH) is a cardinal neuropathology in HIV patients with neuropathic pain. Based on our preliminary studies, we propose that neuroinflammation is a convergent neuropathological mechanism by which gp120 and opioids cooperate to potentiate pathological pain. Our preliminary studies further show that gp120 and morphine elicit neuroinflammation via overlapped but distinct molecular pathways. We hypothesize that morphine and gp120 synergize pain pathogenesis by co-activating the neuroinflammatory pathways. The proposed research is to test this central hypothesis by elucidating the roles of these pathways in pain pathogenesis induced by gp120 and morphine alone or in combination. We will use interdisciplinary approaches of protein analysis, single cell transcriptome analysis, whole cell patch recording and behavioral testing. Results from these studies will significantly improve our understanding of the mechanism by which morphine exacerbates HIV-associated pain.

NARRATIVE Morphine is a common analgesic used by many HIV/AIDS patients, but has the side effect of enhancing pain states. This project will help us better understand how morphine develops this unwanted side effect so that we can design effective approaches to prevent it.