Alcohol最新文献

{"title":"Alcohol use disorder exacerbates clinical and vascular risks differentially in psychiatric disorders","authors":"Eva Christina Meyer ,&nbsp;Younes Adam Tabi","doi":"10.1016/j.alcohol.2025.06.003","DOIUrl":"10.1016/j.alcohol.2025.06.003","url":null,"abstract":"<div><div>Alcohol Use Disorder (AUD) is a major public health concern with detrimental effects on cognitive and neurological function, yet its impact on psychiatric populations remains incompletely defined. In this global propensity score–matched cohort study, we examined the clinical and vascular consequences of comorbid alcohol abuse across diverse psychiatric disorders. Data from the TriNetX network, encompassing electronic medical records from 143 healthcare organizations, were analyzed. For each disorder—anxiety, depression, bipolar disorder, schizophrenia, reaction to severe stress, eating disorders, personality disorders, psychoactive substance dependence, developmental disorders, and obsessive-compulsive disorder—patients with alcohol abuse were matched 1:1 to those without, controlling for demographic and clinical factors. Over a 1095-day follow-up, outcomes evaluated included emergency department visits, pain prevalence, mortality, and cerebrovascular events (transient ischemic attacks and strokes). Alcohol abuse was consistently associated with significantly higher emergency care utilization, increased somatic pain, and elevated mortality across all groups. For instance, anxiety and depression cohorts exhibited 8.1% and 7.3% higher emergency visits and increased mortality by 2.7% and 2.4%, respectively, while schizophrenia showed a twofold increase in stroke risk and markedly higher pain (risk ratio 2.21). These results underscore that AUD exacerbates clinical and vascular risks in psychiatric patients, highlighting the urgent need for targeted interventions.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"127 ","pages":"Pages 85-92"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144328082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Explaining increased efficacy of naltrexone in the treatment of alcohol dependent patients with a family history of alcohol use disorder: A systematic review on the role of reward sensitivity and sweet liking","authors":"Jan van Amsterdam ,&nbsp;Wim van den Brink","doi":"10.1016/j.alcohol.2025.06.004","DOIUrl":"10.1016/j.alcohol.2025.06.004","url":null,"abstract":"<div><div>A positive family history of alcohol use disorder (FHA+) is one of the strongest risk factors for developing alcohol use disorder (AUD) compared. Importantly, naltrexone (NTX) has shown higher efficacy in treating FHA + AUD patients than FHA− AUD patients. Possibly, this may be explained by the attenuation of high reward sensitivity and liking sweet substances (“sweet liking”; SL) in FHA + AUD patients. This systematic review explores whether attenuation by NTX of reward sensitivity and SL explains its higher efficacy in FHA + compared to FHA− AUD patients.</div><div>Separate systematic literature searches were performed on the effect of NTX in FHA + AUD patients, the effect of NTX on reward sensitivity, and the associations of FHA+ with reward sensitivity and SL.</div><div>In total, 36 eligible studies were included (6 for the effect of NTX in FHA + AUD patients, 18 for reward sensitivity, and 12 for sweet liking). In 5 out of 6 studies, a moderating effect of FHA + on NTX treatment efficacy in AUD was shown, with higher efficacy of NTX in FHA + AUD patients. In 6 out of 8 studies, reward sensitivity moderated the treatment effect of NTX in AUD, and in 9 of 10 studies, reward sensitivity was attenuated by NTX. In 3 studies, SL positively moderated the effect of NTX in AUD. Finally, in 9 of 9 studies, SL was attenuated by NTX and enhanced by (partial) opioid agonists.</div><div>Increased reward sensitivity (and sweet-liking as its possible indicator) appeared to be positively associated with FHA+ and was attenuated by NTX, which may (partly) explain the increased effect of NTX in FHA + AUD patients. These results may foster personalized pharmacotherapy in AUD patients.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"127 ","pages":"Pages 63-72"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating TWAS and GWAS identifies gut microbiota–immune interactions to alcohol dependence genetics in European sample","authors":"Haohao Xu ,&nbsp;Peng Shen ,&nbsp;Zhenglin Zhao ,&nbsp;Yushuang Xing ,&nbsp;Tonghui Yi ,&nbsp;Chao Yang ,&nbsp;Han Gao ,&nbsp;Hongyan Guo ,&nbsp;Mingqian Zhao ,&nbsp;Shanbo Zhang ,&nbsp;Di Jia ,&nbsp;Weiming Zhao","doi":"10.1016/j.alcohol.2025.05.006","DOIUrl":"10.1016/j.alcohol.2025.05.006","url":null,"abstract":"<div><h3>Objective</h3><div>Alcohol dependence (AD) is a global public health concern with strong genetic characteristics. The purpose of this study was to explore the underlying pathogenic genes and mechanisms associated with AD.</div></div><div><h3>Methods</h3><div>This study employed a multi-omics Mendelian randomization approach to identify potential disease-causing genes for AD. Specifically, we integrated transcriptome-wide association studies (TWAS) with summary-data-based Mendelian randomization (SMR) to pinpoint candidate genes associated with AD. Additionally, mediating Mendelian randomization was utilized to investigate the mediating role of the gut microbiota in the relationship between immune cell phenotypes and AD.</div></div><div><h3>Results</h3><div>Two susceptibility genes associated with AD, ADH1C and POLI, were identified a joint analysis of SMR and integrated cross-tissue and single tissue TWAS in European population. A new genetic locus associated with AD, rs62307318, was uncovered through cross-organism TWAS. This finding was further validated using Mendelian randomization and Phenome-wide association analysis. Additionally, Mendelian randomization identified Paceibacteria as a possible mediator between Myeloid DC AC and AD.</div></div><div><h3>Conclusion</h3><div>This study identified two genes closely related to AD and explored the possible pathogenesis of AD, which provides a new insight into the treatment and pathogenesis of AD.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"127 ","pages":"Pages 11-20"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144227931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alcohol effects on associative and sensorimotor cortico-thalamo-basal ganglia circuits alter decision making and alcohol intake","authors":"David M. Lovinger","doi":"10.1016/j.alcohol.2025.05.005","DOIUrl":"10.1016/j.alcohol.2025.05.005","url":null,"abstract":"<div><div>Much of the behavioral repertoire of humans and other vertebrates is learned and controlled through the function of brain circuits involving the cortex, thalamus and Basal Ganglia (for simplicity we will refer to this as the Cortico-Thalamo-Basal Ganglia, or CTBG, circuitry). As the name implies, these circuits include the different regions of cortex and thalamus, as well as BG subregions including the striatum, globus pallidus (GP), substantia nigra (SN)/ventral tegmental area (VTA), and the subthalamic nucleus (STN). This circuitry has developed evolutionarily to provide overarching control of actions following discrete environmental events as well as self-initiated actions. Several parallel CTBG circuits have been identified and linked to different aspects of action control under different circumstances. Research in experimental psychology and Neuroscience has established how different CTBG circuits contribute to control of actions based on environmental circumstances and past learning history. There is also a large and growing body of evidence that misused substances, including alcohol, act on cells within these circuits. These actions promote acute intoxication and drug seeking and contribute to changes in behavior induced by chronic alcohol exposure, withdrawal and relapse. Alcohol exposure also influences which of the different CTBG circuits has the strongest influence on behavior. This review will cover the relevant circuitry and describe the current state of knowledge as to how alcohol alters CTBG circuit function and control of behavior. Studies in rodents, non-human primates and humans will be discussed. Finally, ideas for future research directions in this area will be considered.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"127 ","pages":"Pages 21-46"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of high mobility group box 1 pathway inhibition on gene expression in the prefrontal cortex of mice exposed to alcohol","authors":"Shuxun Qiu ,&nbsp;ShuXin Dong ,&nbsp;Jingxin Fan ,&nbsp;Chengji Wu ,&nbsp;Xunzhong Qi","doi":"10.1016/j.alcohol.2024.10.047","DOIUrl":"10.1016/j.alcohol.2024.10.047","url":null,"abstract":"<div><h3>Introduction</h3><div>The high mobility group box 1 (HMGB1) pathway plays a pivotal role in the development of alcohol-induced brain injury. Glycyrrhizinic acid (GlyA) is widely regarded as an inhibitor of HMGB1. The objective is to investigate the impact on gene expression in the prefrontal cortex,we sequenced the transcriptome in control, alcohol-exposed, and HMGB1-inhibited groups of mice. We verified our findings by real-time quantitative PCR (qRT-PCR).</div></div><div><h3>Methods</h3><div>An alcohol exposure model was established in mice by intraperitoneal injection of alcohol. Transcriptome sequencing and bioinformatics analyses were performed on prefrontal cortex tissue. Kyoto Encyclopedia of Genes and Genomes analysis was performed to identify pivotal pathways of differentially expressed genes. The role of relevant genes was verified by qRT-PCR.</div></div><div><h3>Results</h3><div>Expression of genes involved in the neuroactive ligand–receptor interaction pathway exhibited an increase in mice from the alcohol-exposed group. However, there were no significant differences observed in the expression of these genes between control and those receiving an intraperitoneal injection of alcohol along with a HMGB1 inhibitor. Mice in the alcohol-exposed group showed increased gene expression of <em>Cysltr2</em>, <em>Chrna6</em>, <em>Chrna3</em>, <em>Chrnb4</em>, and <em>Pmch</em>. Expression of these genes was decreased in mice injected with HMGB1 inhibitor.</div></div><div><h3>Significance</h3><div>Our study demonstrates that alcohol primarily influences gene expression in the prefrontal cortex of mice through the neuroactive ligand–receptor interaction pathway. HMGB1 inhibitor effectively inhibited the expression of this pathway. This study provides a novel route for drug development in alcohol-induced brain injury.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"127 ","pages":"Pages 47-53"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142592298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Examining the moderating role of intolerance of uncertainty on pain tolerance and craving in patients with chronic pain and alcohol use disorder","authors":"Milena Radoman ,&nbsp;Emily Heilner ,&nbsp;Colleen McGowan ,&nbsp;Benazir Neree-Thompson ,&nbsp;Elcin Sakmar ,&nbsp;Rajita Sinha","doi":"10.1016/j.alcohol.2025.06.001","DOIUrl":"10.1016/j.alcohol.2025.06.001","url":null,"abstract":"<div><div>Chronic pain (CP) and alcohol use disorder (AUD) frequently co-occur, yet the psychological factors underlying their interaction remain unclear. Intolerance of uncertainty (IU) – a cognitive trait linked to distress in unpredictable situations – may influence pain management and coping behaviors in these populations. This study examined whether IU moderates pain and alcohol craving responses to a pain-related stressor in individuals with CP and AUD. Fifty-five adults aged 18–65 years were enrolled, including individuals with CP only (n = 20), AUD only (n = 14), CP + AUD (n = 8), and healthy controls (n = 13). Participants completed a self-report measure of IU and the Yale Pain Stress Test (YPST), an adaptation of the Cold Pressor Test, designed to elicit pain-related stress. Behavioral pain tolerance, subjective pain and alcohol craving were assessed across two experimental sessions, one with exposure to an ice-cold water stressor and the second with a warm-water control condition. Exposure to the pain-related stressor significantly reduced behavioral pain tolerance and increased subjective pain across all groups, and also heightened alcohol craving, particularly in individuals with AUD. IU moderated the pain experience during pain-related stress: in the CP + AUD group, higher IU was associated with lower pain tolerance, whereas in the AUD group, higher IU was correlated with greater pain tolerance. IU also moderated craving responses, with higher IU predicting increased craving in individuals with both CP and AUD. These preliminary findings highlight IU as a potential treatment target, suggesting that interventions aimed at improving uncertainty tolerance may enhance pain coping and reduce stress-driven alcohol-seeking behaviors in vulnerable populations.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"127 ","pages":"Pages 55-61"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ethanol exposure promotes tumor cell migration and angiogenesis in a mouse model of glioblastoma","authors":"Bianca L. Myers ,&nbsp;C. Fernando Valenzuela ,&nbsp;Tou Yia Vue","doi":"10.1016/j.alcohol.2025.05.002","DOIUrl":"10.1016/j.alcohol.2025.05.002","url":null,"abstract":"<div><div>Rapid progression of high-grade gliomas contributes to the poor survival rates of patients, particularly those with aggressive and heterogeneous brain tumors such as glioblastomas (GBMs). Before the onset of tumor symptoms, there exists a vulnerable period during which exposure to environmental factors could exacerbate glioma tumorigenicity. Alcohol (EtOH) is one such factor that has been shown to increase tumor size and vascularization of melanomas in xenograft mouse models and invasion of breast cancer cells in vitro. Currently, whether EtOH exposure promotes glioma progression in vivo is unknown. Here, we induced fluorescently labeled gliomas in immune-competent mice by injecting and electroporating <em>Cre</em> + CRISPR plasmids to delete tumor suppressor genes in neural progenitors lining the right lateral ventricle. Asymptomatic tumor mice were exposed to EtOH or Air vapors via inhalation chambers for five days, followed by two days of rest, then another five days of exposure. This paradigm produced blood ethanol concentrations (BECs) similar to episodic binge drinking, averaging ∼200 mg/dL on the final day of exposure. We found that EtOH exposure acutely increased tumor vascularization and invasion to the contralateral hemisphere. Notably, EtOH-exposed male mice exhibited a significant decrease in survival compared to Air-exposed controls and EtOH-exposed female mice. Overall, our study is the first to demonstrate that developing primary gliomas are susceptible to the tumorigenic effects of EtOH, with males being more vulnerable to increased mortality.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"126 ","pages":"Pages 11-21"},"PeriodicalIF":2.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144048658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An exploratory study of cytokine and inflammatory profiles between young adult low-risk and at-risk drinkers","authors":"Mariann R. Piano ,&nbsp;Shane A. Phillips ,&nbsp;Chueh-Lung Hwang ,&nbsp;Keng-Yu Chang ,&nbsp;Kevin M. Najarro ,&nbsp;Rachel H. McMahan ,&nbsp;Elizabeth J. Kovacs","doi":"10.1016/j.alcohol.2025.05.001","DOIUrl":"10.1016/j.alcohol.2025.05.001","url":null,"abstract":"<div><h3>Background</h3><div>This exploratory study examined plasma levels of pro-inflammatory cytokines, chemokines and growth factors as well as intestinal fatty acid-binding protein (iFABP) and zonulin levels between young adult male and female low-risk and at-risk drinkers.</div></div><div><h3>Methods</h3><div>A total of 33 low-risk (phosphatidylethanol levels &lt;20 ng/ml; 19 female) and 44 at-risk drinkers (phosphatidylethanol levels ≥20 ng/ml; 30 female) were included in this study. Fasting blood samples were obtained in all participants. A multiplex assay was used to measure 48 chemokines and growth factors. An enzyme-linked immunoassay was used to measure plasma levels of human iFABP and zonulin.</div></div><div><h3>Results</h3><div>We found that in young female, at-risk drinkers had a lower level of granulocyte-macrophage colony-stimulating factor (p = 0.04) and platelet-derived growth factor BB (P = 0.04) than low-risk drinkers, while in males, an elevated level of interferon-gamma was found in at-risk drinkers compared to low-risk drinkers (P = 0.04). Intestinal fatty acid-binding protein levels were significantly higher and zonulin levels were significantly lower in at-risk-risk drinkers compared to low-risk drinkers (P = 0.001 and P = 0.02, respectively).</div></div><div><h3>Conclusions</h3><div>These findings suggest that at-risk drinking in young adults is associated with alterations in specific cytokines and proteins involved in intestinal barrier function.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"126 ","pages":"Pages 23-29"},"PeriodicalIF":2.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New developments on the effects of alcohol use on immunity, inflammation and organ function: A summary of the 2024 Alcohol and Immunology Research Interest Group (AIRIG) meeting","authors":"Madison M. Tschann ,&nbsp;Vidula Vachharajani ,&nbsp;Eileen M. Redmond ,&nbsp;Andrew Hoisington ,&nbsp;Sarah E. Cohen ,&nbsp;Moses New-Aaron ,&nbsp;Cristina Llorente ,&nbsp;Janos Paloczi ,&nbsp;Claudia R. Keating ,&nbsp;Wiramon Rungratanawanich ,&nbsp;Ellen L. Burnham ,&nbsp;John J. Callaci ,&nbsp;Preeti Raju ,&nbsp;Weizhe Zhong ,&nbsp;Abhishek Mandal ,&nbsp;Justine R. Zimmerly ,&nbsp;Adriana S.P. Nuncio ,&nbsp;Pranoti Mandrekar ,&nbsp;Rebecca L. McCullough ,&nbsp;Rachel H. McMahan ,&nbsp;Mashkoor A. Choudhry","doi":"10.1016/j.alcohol.2025.04.002","DOIUrl":"10.1016/j.alcohol.2025.04.002","url":null,"abstract":"<div><div>The 29th annual Alcohol and Immunology Research Interest Group (AIRIG) meeting was held on November 22nd, 2024, at Loyola University Chicago, Health Science Campus, Maywood, Illinois. The meeting was divided into three plenary sessions and a poster session. The overall focus of this year’s meeting was on alcohol and host immunity, alcohol and organ dysfunction, and alcohol, inflammation, and tissue injury. The presentations in each session shared the latest developments on the impact of alcohol in a wide variety of fields including trauma, emergency care and hospitalization, cardiovascular health, neurodegenerative disease, gut microbiome, and hepatology.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"126 ","pages":"Pages 1-10"},"PeriodicalIF":2.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143912241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pain in comorbid alcohol use disorder and HIV: A network meta-analysis study","authors":"Muhammed Bishir,&nbsp;Mohamed Sheik Tharik Abdul Azeeze,&nbsp;Sulie L. Chang","doi":"10.1016/j.alcohol.2025.05.003","DOIUrl":"10.1016/j.alcohol.2025.05.003","url":null,"abstract":"<div><div>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 <em>in-vivo</em> for <em>macaques</em> or <em>in-silico</em> 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 <em>Macaca mulatta</em> (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 <em>Macaca mulatta</em> 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, <em>in-silico</em> 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.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"126 ","pages":"Pages 43-53"},"PeriodicalIF":2.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144183144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}