Chronic Binge Alcohol‐induced Hyperalgesia in SIV‐infected Rhesus Macaques

Chronic pain affects more than half of people living with HIV (PLWH), and the current pain management strategies, such as opioids, capsaicin, and gabapentin, remain inefficient in PLWH. Moreover, the pathogenesis of HIV‐associated pain remains widely unknown, hindering implementation of evidence‐based treatments. Alcohol and pain have a bidirectional relationship, where people consume alcohol to relieve pain, and unhealthy alcohol uses leads to chronic pain. Approximately 30% of PLWH develop alcohol use disorder; therefore, it is important to understand the effects of alcohol on pain in this population. Using a relevant preclinical model of HIV‐infection, the aim of the study was to determine if chronic binge alcohol (CBA)‐administration causes hyperalgesia in SIV‐infected macaques. We hypothesized that CBA‐administration causes hyperalgesia in rhesus macaques prior to infection, and these findings will be exacerbated during peak viremia in SIV infection. Rhesus macaques, four to six years old were administered CBA or isovolumetric water (VEH) through an intragastric catheter for 30 minutes, five days a week, with blood alcohol concentrations reaching 50–60 mM. Three months after the start of CBA administration, macaques were inoculated with SIVMac251 and 2.5 months later initiated on antiretroviral therapy. To assess thermal hyperalgesia, tail withdrawal test was used. Conscious macaques were restrained in chairs and their tails are placed in water baths at 40, 50, and 55C, and the latency to remove their tail (in seconds) determined. The test was performed three months after the initiation of CBA administration (24 hours after a CBA administration session), and repeated 2.5 months after SIV‐infection. Molecular analysis for proteins involved in pain circuitry will be determined in the spinal cord and periaqueductal gray. Our results indicate that three months of CBA administration causes hyperalgesia in rhesus macaques. Whether SIV infection exacerbates hyperalgesia, and if the molecular measures correlates to behavioral measures warrants further investigation. These data provide mechanistic insight into how unhealthy alcohol use affects hyperalgesia in HIV infection, and will provide a scientific basis for pain management strategies in this population. Support or Funding Information NIH/NIAAA P60 AA009803 and 5T32AA007577‐19