Pain in comorbid alcohol use disorder and HIV: A network meta-analysis study

Alcohol use is prevalent among people with HIV (PWH). PWH often experience pain (said discomfort) and use alcohol to combat pain. We reported that short-term alcohol exposure exerts analgesic effect. Prolonged exposure is known to result in chronic pain. We hypothesize that alcohol exposure, either in-vivo for macaques or in-silico simulation exposure onto differentially expressed genes (DEGs) from HIV-1Tg rats and HIV patients, exacerbates discomfort in PWH. To substantiate this hypothesis, we analyzed genomic data collected from three brain datasets including the hippocampus of alcohol-exposed Macaca mulatta (GSE69685), HIV-1Tg rats (GSE47474), and post-mortem brain tissue of HIV-positive patients (GSE28160). Ingenuity Pathway Analysis (IPA)-Core Analysis revealed activation of neuroinflammation, neuropathic pain signaling pathways, and the inhibition of opioid signaling as well as in the increase of neuromuscular disease with neuropathy in Macaca mulatta exposed to binge EtOH and SIV infection. IPA-Core Analysis of the DEGs from HIV-1Tg rats, a rat model that mimics HIV patients on cART, possessing 7 of 9 HIV viral proteins, showed activation of neuroinflammation, neuropathic pain signaling pathways. IPA-Core Analysis of the DEGs from HIV patients showed activation of neuroinflammation and inhibition of neuropathic pain and increase in neuromuscular disease with neuropathy. To study the impact of alcohol exposure in HIV-1Tg rats and HIV patients, in-silico simulation of ethanol (EtOH) treatment mimicking exposure of alcohol onto the DEGs in response to HIV viral proteins in HIV-1Tg rats and HIV infection in HIV patients enhanced discomfort and increased neuromuscular diseases. These molecules showed significant modulation by simulated alcohol exposure, further supporting the link between alcohol use and heightened pain in PWH. Taking together, our findings suggest that alcohol consumption and HIV promote pain via modulating signaling pathways including neuroinflammation, and neuropathic pain signaling pathways and by disease like neuromuscular disease with neuropathy.