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

IF 2.5 4区医学 Q3 PHARMACOLOGY & PHARMACY

Alcohol Pub Date : 2025-05-27 DOI:10.1016/j.alcohol.2025.05.003

Muhammed Bishir, Mohamed Sheik Tharik Abdul Azeeze, Sulie L. Chang

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引用次数: 0

Abstract

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.

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伴随酒精使用障碍和HIV的疼痛：一项网络荟萃分析研究

酒精使用在艾滋病毒感染者（PWH）中很普遍。PWH经常感到疼痛（不适），并使用酒精来对抗疼痛。我们报道了短期酒精暴露有镇痛作用。已知长时间接触会导致慢性疼痛。我们假设酒精暴露，无论是猕猴体内暴露，还是在计算机模拟中暴露于来自HIV- 1tg大鼠和HIV患者的差异表达基因（DEGs），都会加剧PWH的不适。为了证实这一假设，我们分析了从三个大脑数据集收集的基因组数据，包括酒精暴露的猕猴（GSE69685）的海马、HIV-1Tg大鼠（GSE47474）和hiv阳性患者（GSE28160）的死后脑组织。独创性途径分析(IPA)-核心分析显示，暴露于暴食EtOH和SIV感染的猕猴的神经炎症、神经性疼痛信号通路的激活和阿片信号的抑制，以及神经肌肉疾病伴神经病变的增加。HIV- 1tg大鼠是一种在cART上模仿HIV患者的大鼠模型，拥有9种HIV病毒蛋白中的7种，其deg的IPA-Core分析显示，神经炎症、神经性疼痛信号通路被激活。HIV患者deg的IPA-Core分析显示，神经炎症激活，神经性疼痛抑制，神经肌肉疾病伴神经病增加。为了研究酒精暴露对HIV- 1tg大鼠和HIV患者的影响，硅模拟乙醇（EtOH）治疗模拟酒精暴露于HIV- 1tg大鼠的deg对HIV病毒蛋白的反应，以及HIV患者的HIV感染会增加不适和增加神经肌肉疾病。这些分子通过模拟酒精暴露表现出显著的调节，进一步支持酒精使用与PWH疼痛加剧之间的联系。综上所述，我们的研究结果表明，饮酒和艾滋病毒通过调节信号通路（包括神经炎症、神经性疼痛信号通路）和神经肌肉疾病（如神经病变）等疾病来促进疼痛。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Alcohol 医学-毒理学

CiteScore

4.60

自引率

4.30%

发文量

审稿时长

15.6 weeks

期刊介绍： Alcohol is an international, peer-reviewed journal that is devoted to publishing multi-disciplinary biomedical research on all aspects of the actions or effects of alcohol on the nervous system or on other organ systems. Emphasis is given to studies into the causes and consequences of alcohol abuse and alcoholism, and biomedical aspects of diagnosis, etiology, treatment or prevention of alcohol-related health effects. Intended for both research scientists and practicing clinicians, the journal publishes original research on the neurobiological, neurobehavioral, and pathophysiological processes associated with alcohol drinking, alcohol abuse, alcohol-seeking behavior, tolerance, dependence, withdrawal, protracted abstinence, and relapse. In addition, the journal reports studies on the effects alcohol on brain mechanisms of neuroplasticity over the life span, biological factors associated with adolescent alcohol abuse, pharmacotherapeutic strategies in the treatment of alcoholism, biological and biochemical markers of alcohol abuse and alcoholism, pathological effects of uncontrolled drinking, biomedical and molecular factors in the effects on liver, immune system, and other organ systems, and biomedical aspects of fetal alcohol spectrum disorder including mechanisms of damage, diagnosis and early detection, treatment, and prevention. Articles are published from all levels of biomedical inquiry, including the following: molecular and cellular studies of alcohol''s actions in vitro and in vivo; animal model studies of genetic, pharmacological, behavioral, developmental or pathophysiological aspects of alcohol; human studies of genetic, behavioral, cognitive, neuroimaging, or pathological aspects of alcohol drinking; clinical studies of diagnosis (including dual diagnosis), treatment, prevention, and epidemiology. The journal will publish 9 issues per year; the accepted abbreviation for Alcohol for bibliographic citation is Alcohol.