Alcohol最新文献

{"title":"The Majchrowicz binge model of alcohol dependence: A valid model for comparing male and female rats","authors":"S.A. Collins,&nbsp;S.P. Guerin,&nbsp;N.N. Nawarawong,&nbsp;E.R. Carlson,&nbsp;K.R. Thompson,&nbsp;K. Nixon","doi":"10.1016/j.alcohol.2025.08.003","DOIUrl":"10.1016/j.alcohol.2025.08.003","url":null,"abstract":"<div><div>Alcohol use disorders (AUD) among women have steadily risen over the past decade. This increase is due in part to increased rates of drinking among some populations of women, yet relatively little is known about alcohol in women. Until recently, the majority of clinical and preclinical studies investigating AUD have focused on these effects in males, including in the Majchrowicz binge model of alcohol dependence. Therefore, the objective of this study was to perform a retrospective analysis of intoxication behavior and withdrawal severity in adult male and female Sprague Dawley rats using the Majchrowicz model. Rats were gavaged intragastrically with ethanol diet every 8 h for 4 days with doses titrated based on the rat's intoxication behavior. Ten hours after the final dose of alcohol, withdrawal behavior was assessed for 17 h. Males were slightly more intoxicated behaviorally than females, which resulted in females receiving a slightly larger dose of ethanol per day. Despite these differences in intoxication behavior, similar blood ethanol concentrations (BECs) and withdrawal behaviors were observed for males and females. Altogether, these data suggest that while slight differences in intoxication and therefore dosing occur in the Majchrowicz model of alcohol dependence, the model reliably produces similar BECs and minimizes differences in withdrawal severity. This is further supported by a principal component analysis, which confirmed moderate overlap between sexes based on these parameters. Thus, this model is useful for making direct comparisons between groups, and here between sexes, where slight differences in ethanol pharmacokinetics are known to occur.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"129 ","pages":"Pages 41-49"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982189","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":"Sex differences in the impact of trauma on alcohol self-administration","authors":"Nabiha Mahmood ,&nbsp;Marian L. Logrip","doi":"10.1016/j.alcohol.2025.09.006","DOIUrl":"10.1016/j.alcohol.2025.09.006","url":null,"abstract":"<div><div>Challenging encounters can lead to escalated alcohol consumption, as evidenced by individuals grappling with posttraumatic stress disorder (PTSD). However, the precise influence of prior stress experiences, as opposed to acute stressors, on alcohol intake remains incompletely understood. This study sought to simulate the enduring repercussions of trauma using a stress paradigm involving foot shocks presented in an odor-enriched environment. The presence of a scent throughout contextual fear conditioning is more likely to cause stress effects to generalize across various environments, and this paradigm previously reduced working memory performance, one hallmark of PTSD. Male and female Wistar rats were exposed to the stress or control condition (no foot shock), then trained to perform lever presses to obtain alcohol reinforcement. The findings revealed intriguing disparities between the sexes in past stress effects on the acquisition of alcohol self-administration. Specifically, female rats exhibited divergent patterns of alcohol acquisition across days, with the control group showing a swifter acquisition compared to their previously stressed counterparts. This pattern was not observed in males, nor did either sex show differences in relapse-like self-administration after a 5-week abstinence period. Unexpectedly, presentation of the stress session odor cue did not alter alcohol self-administration behavior. Together, these data support heightened sensitivity of females to a trauma-like stressor, although in rats this decreased self-administration, contrary to human data.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"129 ","pages":"Pages 106-114"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182363","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":"N-acetylcysteine prevents ethanol-induced neuropathic pain by downregulating nociceptive activation of supraspinal brain areas","authors":"Natália Gabriele Hösch ,&nbsp;Raíssa A.F. Reis ,&nbsp;Rômulo Dias Novaes ,&nbsp;Carlos Giovani O. Nascimento ,&nbsp;Renato Rizo Ventura ,&nbsp;Silvia Graciela Ruginsk ,&nbsp;Jalile Amin-Naves","doi":"10.1016/j.alcohol.2025.10.003","DOIUrl":"10.1016/j.alcohol.2025.10.003","url":null,"abstract":"<div><div>Considering the important clinical applications of N-acetylcysteine (NAC), the present study investigated the effects of NAC treatment on ethanol-induced neuropathic alterations. For this purpose, a total number of eighty-one male adult Wistar rats were used. Alcoholic neuropathy was induced by administration of 38 % (v/v) ethanol (10 g/kg/day, oral gavage) for 10 weeks. NAC solution (1.4 g/kg/day, oral gavage) was administered immediately after ethanol treatment, also for 10 weeks. The electronic von Frey, Randall Selitto and tail flick tests were used to characterize the nociceptive thresholds to mechanical and thermal stimulations. The Rota-rod test was used to evaluate motor coordination, whereas the open field test was employed to assess general locomotor activity. The present study also determined the integrity of the sciatic nerve and the number of c-Fos immunoreactive neurons in key brain structures. As expected, long-term exposure to ethanol reduced the thickness of myelin sheath in the peripheral nerve, as well as induced allodynia, mechanical and thermal hypernociception, as well as motor incoordination. Although ethanol treatment did not alter general locomotor activity, it increased the number of rearing events, indicating enhanced exploratory behavior. In the brain, chronic ethanol consumption was associated with higher levels of c-Fos expression in the dorsal raphe nucleus, parvocellular and magnocellular groups of the hypothalamic paraventricular nucleus, and also in the periaqueductal gray. Consistent with its protective effects, NAC treatment prevented the development of all ethanol-induced alterations, including at central level. Taken together, these results suggest that NAC consistently prevents ethanol-induced neuropathy.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"129 ","pages":"Pages 134-144"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145276754","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":"Chronic alcohol drinking delays recovery from capsaicin- and nerve injury-induced hypersensitivity in mice","authors":"Rachel Schorn ,&nbsp;Maureen Riedl ,&nbsp;Laura S. Stone ,&nbsp;Anna M. Lee ,&nbsp;Lucy Vulchanova","doi":"10.1016/j.alcohol.2025.10.001","DOIUrl":"10.1016/j.alcohol.2025.10.001","url":null,"abstract":"<div><div>Chronic pain and alcohol use disorder (AUD) are major health concerns that significantly impair quality of life. Persistent pain is common in individuals with alcohol dependence, and alcohol is commonly used by chronic pain patients for self-medication. The neural mechanisms linking these conditions remain unclear. We hypothesized that chronic alcohol exposure induces hypersensitivity in multiple modalities and increases the duration of recovery in acute and persistent pain models. Using the two-bottle free-choice alcohol consumption paradigm in adult mice, alcohol-induced hypersensitivity (AIH), indicated by reduced mechanical withdrawal thresholds, developed after 4–6 weeks of alcohol consumption compared to age- and sex-matched water-consuming controls. Alcohol-consuming female mice, but not male mice, developed cold hypersensitivity after AIH emerged. To assess the impact of chronic alcohol consumption on acute and persistent pain, we used intraplantar capsaicin and sciatic nerve crush models, respectively. In the capsaicin model, water-treated, but not alcohol-treated, mice recovered from hypersensitivity by 24 h post-injection. In the sciatic nerve crush model, alcohol-consuming mice exhibited slower recovery of mechanical withdrawal thresholds compared to water-consuming controls. While mechanical hypersensitivity in water-consuming mice returned to pre-surgical thresholds by 3–4 weeks post-surgery, recovery in alcohol-consuming mice was both delayed and partial. Surgical intervention did not impact alcohol intake. Overall, our results suggest that chronic voluntary alcohol consumption facilitates the transition to chronic pain by prolonging hypersensitivity and delaying recovery from injuries.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"129 ","pages":"Pages 123-133"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145240610","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":"Contributions of testosterone to excessive alcohol drinking in males: Potential role for interactions with the HPA axis","authors":"Roman A. Zegarelli,&nbsp;Anna K. Radke","doi":"10.1016/j.alcohol.2025.09.005","DOIUrl":"10.1016/j.alcohol.2025.09.005","url":null,"abstract":"<div><div>Excessive alcohol drinking and alcohol use disorders (AUDs) are a significant and increasing public health concern in the United States and worldwide, with men historically having higher rates of alcohol consumption and AUD diagnoses. Despite this, the biological mechanisms underlying sex differences in these outcomes are not fully understood. Endocrine systems are critical regulators of behavior and testosterone has a bidirectional relationship with alcohol in males. Baseline levels of testosterone (T) may bias males toward approach behaviors that increase the tendency to engage in risky drinking behaviors in adolescent and adult men. At the same time, T appears to protect males (particularly rodents) against elevated levels of initial alcohol consumption. T levels also change with alcohol exposure, decreasing with acute and chronic use. This review synthesizes findings from both human and animal studies, highlighting how interactions between the hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-adrenal (HPA) axes may underlie male-specific patterns of alcohol use and risk for AUD. Understanding these mechanisms is essential for preclinical and clinical researchers conducting research in males and for the development of more effective interventions for AUD in men.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"129 ","pages":"Pages 92-105"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145118967","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":"Intermittent short- and long-term alcohol exposures influence alcohol consumption, anxiety-like behaviors, and seizure onset in genetically epilepsy-prone rats","authors":"Gleice Kelli Silva-Cardoso,&nbsp;Prosper N'Gouemo","doi":"10.1016/j.alcohol.2025.10.002","DOIUrl":"10.1016/j.alcohol.2025.10.002","url":null,"abstract":"<div><div>The genetically epilepsy-prone rats (GEPR-3s) are known for their hereditary susceptibility to seizures and anxiety. This study investigates the impact of short-term (1 week) and long-term (4 weeks) intermittent alcohol exposure through a two-bottle choice paradigm on voluntary alcohol intake, anxiety-like behaviors, and acoustically evoked seizure susceptibility in the GEPR-3s. Anxiety behaviors were assessed 24 h post alcohol exposure using the light-dark box (LDB), open field (OFT), and elevated plus maze (EPM), alongside evaluations of seizure susceptibility. The results indicated that after 1 week of alcohol exposure, female GEPR-3s had higher alcohol intake and preference than males, while males increased their intake and preference after 4 weeks. Furthermore, females GEPR-3s exhibited anxiolytic effects in all anxiety tests after short-term alcohol exposure. In contrast, males displayed mixed responses, exhibiting anxiogenic effects in both LDB and OFT tests, and increased time in open arms but decreased exploration in the EPM test. Further, short-term alcohol exposure delayed seizure onset across both sexes, suggesting potential anticonvulsant effects. After 4 weeks of alcohol exposure, male GEPR-3s exhibited anxiogenic effects in both LDB and OFT tests, and reduced locomotion in the EPM test. In contrast, female GEPR-3ss showed anxiogenic effects in the LDB test, but anxiolytic effects in the OFT test, with decreased locomotion in the EPM test. Additionally, long-term alcohol exposure decreased seizure latency, indicating proconvulsant effects. These findings highlight the complex, bidirectional, and temporal dynamics between alcohol consumption, anxiety, and inherited predisposition to epilepsy.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"129 ","pages":"Pages 115-122"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145234385","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 use disorder-associated pain: clinical and preclinical evidence","authors":"Yuyang Dong,&nbsp;Matthew W. Buczynski,&nbsp;Ann M. Gregus","doi":"10.1016/j.alcohol.2025.08.005","DOIUrl":"10.1016/j.alcohol.2025.08.005","url":null,"abstract":"<div><div>Alcohol Use Disorder (AUD) affects millions of people globally and is characterized by cycles of intoxication, withdrawal, and relapse. Convergent clinical and preclinical evidence strongly support the conclusion that AUD precipitates chronic pain marked by mechanical and thermal hypersensitivity, yet currently available FDA-approved therapeutics do not effectively manage AUD-associated pain. This review synthesizes clinical and preclinical evidence on AUD-associated pain, highlighting known phenomena of allodynia and hyperalgesia as well as small and/or large fiber neuropathy in patient subpopulations along with preclinical acute and chronic alcohol exposure paradigm-specific nociceptive phenotypes in rodents. Herein, we provide detailed descriptions and interpretations of outcome measures for different sensory modalities typically utilized in clinical and/or preclinical studies of nociception. We examine how these endpoints vary in rodent models according to the type of alcohol exposure paradigm with regard to route of administration, chronicity, and contingency (forced, voluntary, or combined). Finally, we summarize the prominent molecular mechanisms that have been proposed to mediate alcohol withdrawal-induced pain-like behaviors. While major advances have been made in treatment of AUD, critical gaps in understanding of human pain phenotypes due to lack of quantitative endpoints in clinical trials impede further advancement in refining preclinical models to recapitulate these features. Patient phenotype-driven preclinical models will increase cross-species translational potential for interrogating mechanistic underpinnings and thereby inform future drug discovery campaigns for treatment of AUD-associated pain.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"129 ","pages":"Pages 14-40"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144989833","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":"Low level alcohol consumption is associated with lower regional brain volume and thickness and lower choline-containing compounds and myo-inositol levels in healthy adults","authors":"Timothy C. Durazzo ,&nbsp;Brian D.P. Joseff ,&nbsp;Dieter J. Meyerhoff","doi":"10.1016/j.alcohol.2025.10.007","DOIUrl":"10.1016/j.alcohol.2025.10.007","url":null,"abstract":"<div><div>Low levels of alcohol consumption (e.g., up to two standard drink equivalents/day for males and one drink/day for females) have been viewed as benign or even beneficial, particularly for cardiovascular function. A limited number of studies investigated associations of alcohol consumption with brain volumes and metabolite levels in “healthy” cohorts without alcohol use disorder (AUD) and yielded mixed results. To date, no study has concurrently assessed brain morphometrics and metabolites in regions that previously showed associations with alcohol consumption in healthy adults. The current study examined the associations between alcohol consumption and magnetic resonance measures of brain volume and cortical thickness (n = 44), and brain metabolite levels (n = 27–29) in healthy non-smoking adults (22–70 years of age) with no history of AUD; average number of drinks/month prior to study was 19 ± 17. Volumes and thickness were quantitated for the bilateral anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC), and metabolites in the ACC and right DLPFC. All participants consumed ≤60 standard drink equivalents per month, over the year preceding study. Lower left caudal ACC volume and thickness and lower right superior frontal gyrus volume were related to higher 1-year average drinks/month. Lower ACC creatine-containing compounds and <em>myo</em>-inositol levels were associated with higher 1-year average drinks/month; lower ACC <em>myo</em>-inositol concentration was related to higher lifetime average drinks/month. Results indicate potential neurobiological consequences for levels of alcohol consumption currently considered “low risk” for adverse biomedical effects. These findings may have implications for current harm reduction strategies and alcohol consumption public health guidelines.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"129 ","pages":"Pages 157-165"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145412583","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":"Impact of adolescent ethanol binge on serotonin signaling and pain sensitivity post-withdrawal","authors":"Alexander James Feller ,&nbsp;Louis John Kolling ,&nbsp;Tien Tran ,&nbsp;Shafa Ismail ,&nbsp;Jessica Marie Hunter Alberhasky ,&nbsp;Samuel Cole Luciano ,&nbsp;Catherine Anne Marcinkiewcz","doi":"10.1016/j.alcohol.2025.09.001","DOIUrl":"10.1016/j.alcohol.2025.09.001","url":null,"abstract":"<div><div>Adolescence is a critical neurodevelopmental period characterized by heightened neuroplasticity. While the acute effects of binge ethanol (EtOH) consumption are documented, its long-term impact on both pain sensitivity and microglial activation during adolescence remains unclear. Given serotonin's (5-HT) known involvement in pain processing and sensitivity to EtOH, this study examined the effects of adolescent EtOH binge on microglia-induced neuroinflammation in serotonergic nuclei, downstream 5-HT signaling, and pain sensitivity at different time points after EtOH withdrawal. Adolescent male C57BL/6J mice received triweekly oral gavage of 20 % EtOH or water for 4 weeks and were assessed after 24 h and 3 weeks post-withdrawal. We used immunohistochemistry to assess neuroinflammation in the dorsal raphe, median raphe, and raphe magnus by labeling 5-HT, CD68, and P2Y12. Further analyses examined downstream signaling via 5-HT and serotonin transporter (SERT) expression in the nucleus accumbens, anterior cingulate cortex, thalamus, amygdala, hypothalamus, and raphe magnus. Pain sensitivity was then assessed using the Hargreaves test. EtOH exposure led to widespread serotonergic and neuroinflammatory changes. Significant increases in microglia-induced neuroinflammation were observed in the dorsal raphe nucleus, median raphe nucleus, and raphe magnus nucleus after both 24 h and 3 weeks post-withdrawal, along with significant deficits in 5-HT. Similar 5-HT deficits were observed in downstream regions—notably in the anterior cingulate cortex, thalamus, amygdala, and hypothalamus—at varying time points post-withdrawal. EtOH-exposed mice also showed lasting hyperalgesia at both 24 h and 3 weeks post-withdrawal that persisted for up to 9 weeks. These results suggest that persistent hyperalgesia following adolescent EtOH binge may be driven by changes in serotonergic function and microglial activation.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"129 ","pages":"Pages 58-68"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145056617","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":"Ibudilast attenuates the association between pain intensity and heavy drinking in alcohol use disorder: A secondary analysis of a randomized clinical trial","authors":"Steven J. Nieto ,&nbsp;Erica N. Grodin ,&nbsp;Lara A. Ray","doi":"10.1016/j.alcohol.2025.10.004","DOIUrl":"10.1016/j.alcohol.2025.10.004","url":null,"abstract":"<div><h3>Background</h3><div>Pain frequently co-occurs with alcohol use disorder (AUD) and may influence treatment response. In this secondary analysis of a completed randomized clinical trial, we examined whether baseline pain intensity and pain-related disability moderate the effects of ibudilast, a neuroimmune-modulating agent, on drinking outcomes over 12 weeks.</div></div><div><h3>Method</h3><div>Participants (N = 102; 60 % male; <em>M</em> age = 44.26, <em>SD</em> = 10.81) with moderate-to-severe AUD were randomized to ibudilast (50 mg twice daily) or placebo for 12 weeks. Pain intensity and disability were assessed at baseline using the Graded Chronic Pain Scale. Piecewise linear mixed-effects models tested the moderating effect of pain on percent heavy drinking days (PHDD), percent days abstinent, drinks per day, and drinks per drinking day, adjusting for early (baseline–Week 2) and late (Weeks 4–12) trial phases.</div></div><div><h3>Results</h3><div>Pain variables were not significantly correlated with any drinking outcome at baseline (all |<em>r</em>| ≤ .08, <em>p</em> &gt; .45). Significant three-way interactions (Medication × Pain Intensity × Time) emerged for PHDD in both early and late phases (<em>p</em>s &lt; 0.05), indicating that higher pain intensity predicted greater PHDD in the placebo arm (<em>b</em> = 0.10, <em>p</em> = .04) but not in the ibudilast arm (<em>b</em> = 0.007, <em>p</em> ≥ .89). Similar interactions were observed for pain intensity and pain-related disability on drinks per day, though simple slopes were nonsignificant. No significant moderation effects were found for percent days abstinent or drinks per drinking day.</div></div><div><h3>Conclusions</h3><div>Ibudilast attenuated the positive association between baseline pain intensity and heavy drinking, suggesting that pain intensity may identify an AUD subgroup more likely to benefit from neuroimmune-targeted pharmacotherapy. These findings support incorporating pain phenotyping into AUD treatment research and point toward a precision medicine approach to enhance treatment efficacy.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"129 ","pages":"Pages 145-149"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145294528","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}