AlcoholPub Date : 2025-10-22DOI: 10.1016/j.alcohol.2025.10.005
Karolina Dorobisz , Tadeusz Dorobisz , Katarzyna Pazdro-Zastawny , Marzena Janczak , Katarzyna Czyż
{"title":"The impact of alcohol addiction on the quality of life, mental condition, clinical condition and nutritional status of patients with head and neck cancer","authors":"Karolina Dorobisz , Tadeusz Dorobisz , Katarzyna Pazdro-Zastawny , Marzena Janczak , Katarzyna Czyż","doi":"10.1016/j.alcohol.2025.10.005","DOIUrl":"10.1016/j.alcohol.2025.10.005","url":null,"abstract":"<div><h3>Introduction</h3><div>Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, with over 880,000 new cases reported worldwide each year. Tobacco smoking and alcohol drinking are the main risk factors for HNSCC, accounting for 30 % of HNSCC cases worldwide. Alcohol is a particularly important risk factor not only for HNSCC and was recognized in 1988 by the International Agency for Research on Cancer (IARC) as a very important risk factor for the incidence of oral cavity, oropharyngeal, hypopharyngeal and laryngeal cancers, and was classified as group 1 cancer risk factors. The aim of the study was to assess the impact of alcohol on the quality of life, mental state, clinical state and nutritional status in patients with HNSCC.</div></div><div><h3>Material and method</h3><div>The single-center, prospective study included a group of 123 patients aged 42 to 89, treated for laryngeal cancer, pharyngeal cancer and cancer of unknown primary site HNSCC. Socio-demographic data and the presence of risk factors were assessed in each patient. The performance status of the patients was assessed using the Eastern Cooperative Oncology Group (ECOG) scale. The nutritional status of patients was assessed via a Body Mass Index (BMI) assessment and Mini Nutritional Assessment Short FORM (MNA-SF). Each patient was also assessed using the Nutrition Risk Screening 2002 (NRS2002). The level of depression and anxiety was assessed using the Hospital Anxiety and Depression Scale (HADS). Patients were also assessed for sleep problems using the Insomnia Severity Index. Quality of life was assessed using the Polish version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Head and Neck Cancer 35 (EORTC QLQ-H&N35). In each patient, the results of laboratory tests were also analyzed - morphology, nutritional parameters - total protein, total cholesterol and CRP protein level.</div></div><div><h3>Results</h3><div>Patients who regularly drank alcohol more often suffered from throat cancer (91.2 %) and larynx cancer (59.2 %), while CUP was more often diagnosed in patients without a history of regular alcohol consumption. Patients who drank alcohol were diagnosed at a significantly higher stage compared to the group of non-drinkers. In the study group of patients regularly drinking alcohol with diagnosed HSCC, a significantly worse clinical condition, risk of malnutrition or malnutrition was demonstrated compared to patients with diagnosed HNSCC who did not drink alcohol. In laboratory tests, patients drinking alcohol had a lower hemoglobin level before treatment (11.7 vs 12.8 g/dl, p < 0.001), a higher leukocyte level (10.3 vs 7.5 × 10 <sup>9</sup>/l, p < 0.001), a lower total protein level (6.3 vs 6.8 g/dl, p < 0.001), a higher mean CRP level (8.0 vs 5.0 mg/l) and a lower total cholesterol level (134 vs 187 mg/dl, p < 0.001). Those who drank alcohol more often had significan","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"129 ","pages":"Pages 150-156"},"PeriodicalIF":2.9,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145358143","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}
AlcoholPub Date : 2025-10-12DOI: 10.1016/j.alcohol.2025.10.004
Steven J. Nieto , Erica N. Grodin , Lara A. Ray
{"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 , Erica N. Grodin , 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> > .45). Significant three-way interactions (Medication × Pain Intensity × Time) emerged for PHDD in both early and late phases (<em>p</em>s < 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":"2025-10-12","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}
AlcoholPub Date : 2025-10-08DOI: 10.1016/j.alcohol.2025.10.003
Natália Gabriele Hösch , Raíssa A.F. Reis , Rômulo Dias Novaes , Carlos Giovani O. Nascimento , Renato Rizo Ventura , Silvia Graciela Ruginsk , Jalile Amin-Naves
{"title":"N-acetylcysteine prevents ethanol-induced neuropathic pain by downregulating nociceptive activation of supraspinal brain areas","authors":"Natália Gabriele Hösch , Raíssa A.F. Reis , Rômulo Dias Novaes , Carlos Giovani O. Nascimento , Renato Rizo Ventura , Silvia Graciela Ruginsk , 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":"2025-10-08","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}
AlcoholPub Date : 2025-10-04DOI: 10.1016/j.alcohol.2025.10.001
Rachel Schorn , Maureen Riedl , Laura S. Stone , Anna M. Lee , Lucy Vulchanova
{"title":"Chronic alcohol drinking delays recovery from capsaicin- and nerve injury-induced hypersensitivity in mice","authors":"Rachel Schorn , Maureen Riedl , Laura S. Stone , Anna M. Lee , 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":"2025-10-04","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}
AlcoholPub Date : 2025-10-03DOI: 10.1016/j.alcohol.2025.10.002
Gleice Kelli Silva-Cardoso, Prosper N'Gouemo
{"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, 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":"2025-10-03","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}
AlcoholPub Date : 2025-09-25DOI: 10.1016/j.alcohol.2025.09.006
Nabiha Mahmood , Marian L. Logrip
{"title":"Sex differences in the impact of trauma on alcohol self-administration","authors":"Nabiha Mahmood , 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":"2025-09-25","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}
AlcoholPub Date : 2025-09-20DOI: 10.1016/j.alcohol.2025.09.005
Roman A. Zegarelli, Anna K. Radke
{"title":"Contributions of testosterone to excessive alcohol drinking in males: Potential role for interactions with the HPA axis","authors":"Roman A. Zegarelli, 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":"2025-09-20","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":"Molecular mechanism underlying alcohol's residual effects: The role of acetaldehyde in mitochondrial dysfunction at synapses in mouse brain cortex","authors":"Analía G. Karadayian , Lautaro Carrere , Analia Czerniczyniec , Silvia Lores-Arnaiz","doi":"10.1016/j.alcohol.2025.09.004","DOIUrl":"10.1016/j.alcohol.2025.09.004","url":null,"abstract":"<div><div>Alcohol residual effects impose significant physiological and cognitive burdens due to acute ethanol exposure; however, its underlying mechanisms remain poorly understood. This study investigates the role of acetaldehyde, the main ethanol metabolite, in driving mitochondrial dysfunction and synaptic impairment during hangover onset. Using a mice model, we evaluated the effects of ethanol (3.8 g/kg) and the alcohol dehydrogenase inhibitor 4-methylpyrazole (4-MP) on brain cortex synaptosomes.</div><div>Ethanol exposure significantly elevated serum acetaldehyde compared with control (p < 0.05), and induced mitochondrial dysfunction, as evidenced by impaired respiration (30 % decrease in basal O<sub>2</sub> uptake vs. control), mitochondrial membrane depolarization and reduced ATP production (50 % decrease vs. control). These effects were mitigated by pre-treatment with 4-MP, which normalized acetaldehyde levels and partially restored mitochondrial function. Notably, ethanol downregulated synaptic proteins (nNOS, GluN2B, PSD-95; p < 0.05), but 4-MP failed to prevent this reduction, suggesting that acetaldehyde would not be involved in synaptic proteins alterations. Further, ethanol disrupted calcium homeostasis and nitric oxide (NO) content. Interestingly, 4-MP alone also reduced calcium uptake and NO content (p < 0.05), indicating potential off-target effects on neuronal signaling.</div><div>While the reduction in acetaldehyde levels preserved mitochondrial integrity, its inability to rescue synaptic protein loss highlights the complexity of hangover pathology, involving both acetaldehyde-dependent and -independent mechanisms. Our findings underscore acetaldehyde's pivotal role in hangover-associated mitochondrial dysfunction but reveal divergent pathways in synaptic impairment. These insights advance the search for targeted hangover therapies by delineating acetaldehyde-dependent toxicity.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"129 ","pages":"Pages 79-91"},"PeriodicalIF":2.9,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092869","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}
AlcoholPub Date : 2025-09-17DOI: 10.1016/j.alcohol.2025.09.003
Mitchell A. Nothem, Christine M. Side, Simon C. Tran, Anaahat Brar, Lauren A. Buck, Jacqueline M. Barker
{"title":"Chronic pain increases sensitivity to pain-induced reinstatement of ethanol seeking in male mice","authors":"Mitchell A. Nothem, Christine M. Side, Simon C. Tran, Anaahat Brar, Lauren A. Buck, Jacqueline M. Barker","doi":"10.1016/j.alcohol.2025.09.003","DOIUrl":"10.1016/j.alcohol.2025.09.003","url":null,"abstract":"<div><div>Alcohol use disorder (AUD) and chronic pain are complex and debilitating conditions that are highly comorbid. Greater than 50 % of individuals with AUD have chronic pain. Clinical data suggest that people with chronic pain are more likely to report using alcohol to manage chronic pain, and that magnitude of pain is correlated with relapse probability after a period of abstinence. These data led to the hypothesis that pain can drive ethanol seeking and reinstatement in a rodent model of chronic neuropathic pain. A conditioned place preference (CPP) paradigm was used to model ethanol seeking in male C57BL6J mice with a spared nerve injury (SNI). Mice were conditioned with doses of ethanol previously found to reverse pain behavior (0.5 g/kg). Mice with and without SNI showed similar magnitudes of ethanol CPP and rates of extinction. To investigate pain-induced relapse-related behavior, mice underwent reinstatement testing following painful mechanical stimulation which was delivered at either a “moderate” or “high” intensity immediately prior to return to the CPP apparatus. “Moderate” painful hindpaw stimulation reinstated ethanol seeking behavior in SNI-injured, but not sham, mice, while “high” intensity stimulation reinstated ethanol seeking in mice regardless of injury status. These data suggest that males in chronic pain are more susceptible reinstatement of ethanol seeking following a painful experience.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"129 ","pages":"Pages 69-78"},"PeriodicalIF":2.9,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145093341","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}
AlcoholPub Date : 2025-09-10DOI: 10.1016/j.alcohol.2025.09.001
Alexander James Feller , Louis John Kolling , Tien Tran , Shafa Ismail , Jessica Marie Hunter Alberhasky , Samuel Cole Luciano , Catherine Anne Marcinkiewcz
{"title":"Impact of adolescent ethanol binge on serotonin signaling and pain sensitivity post-withdrawal","authors":"Alexander James Feller , Louis John Kolling , Tien Tran , Shafa Ismail , Jessica Marie Hunter Alberhasky , Samuel Cole Luciano , 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":"2025-09-10","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}