Schorn Rachel, Riedl Maureen, Stone Laura S, Lee Anna M, Vulchanova Lucy
bioRxiv. 2025 Sep 11:2025.09.05.674513. doi: 10.1101/2025.09.05.674513.
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 hours 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.
Magnitude of alcohol-induced mechanical hypersensitivity is similar across sexFemales, but not males, develop alcohol-induced cold sensitivityChronic alcohol prolongs acute inflammatory painChronic alcohol prolongs nerve-injury induced neuropathic pain.
慢性疼痛和酒精使用障碍（AUD）是严重影响生活质量的主要健康问题。持续性疼痛在酒精依赖个体中很常见，而慢性疼痛患者常用酒精进行自我治疗。连接这些病症的神经机制仍不清楚。我们假设，慢性酒精暴露会在多种模式下诱发超敏反应，并增加急性和持续性疼痛模型中的恢复持续时间。在成年小鼠中使用双瓶自由选择酒精消耗范式，与年龄和性别匹配的饮水对照相比，饮酒4-6周后出现酒精诱导的超敏反应（AIH），表现为机械性撤腿阈值降低。出现AIH后，饮酒的雌性小鼠（而非雄性小鼠）出现冷超敏反应。为了评估慢性酒精消耗对急性和持续性疼痛的影响，我们分别使用了足底注射辣椒素和坐骨神经挤压模型。在辣椒素模型中，注射后24小时，接受水处理而非酒精处理的小鼠从超敏反应中恢复。在坐骨神经挤压模型中，与饮水对照相比，饮酒小鼠的机械性撤腿阈值恢复较慢。虽然饮水小鼠的机械性超敏反应在手术后3-4周恢复到手术前阈值，但饮酒小鼠的恢复既延迟又不完全。手术干预不影响酒精摄入量。总体而言，我们的结果表明，慢性自愿饮酒通过延长超敏反应和延迟损伤恢复促进向慢性疼痛的转变。
酒精诱导的机械性超敏反应程度在性别间相似
雌性而非雄性出现酒精诱导的冷敏感性
慢性酒精延长急性炎症性疼痛
慢性酒精延长神经损伤诱导的神经性疼痛
