Characterizing the effects of family history of alcoholism on alcohol analgesia

项目摘要 疼痛是患者寻求医疗服务的最常见原因。急性疼痛是一个基本的指标 当前或即将发生的组织损伤。然而，慢性疼痛是一种具有强烈情感的适应不良状态， 生物和心理成分。慢性疼痛的代价极其高昂，并对 患者的生活质量。现有的治疗慢性疼痛的方法，包括阿片类止痛药，相对 效果不佳。可能是由于缺乏有效的治疗方法，最近有报道称，近 25%患有慢性口腔和/或肌肉骨骼疼痛的人通过口服自我用药 饮酒。事实上，酒精与一系列相关的药理靶点相互作用 来调节痛苦的体验。然而，这种直觉互动背后的生物学机制 都没有得到很好的确立。了解这种关系是很重要的，因为酒精止痛可能起到 酒精摄入的强效负性增强剂，这反过来可能会增加风险，从而对健康产生不利影响 患上酒精使用障碍的可能性。酗酒的家庭风险，以及性行为和某些情绪/个性 这些因素可能是个体对酒精镇痛敏感性的关键调节因子。不过，目前 不清楚这种敏感性是否是神经生物学和/或后天因素的结果。通过刻画 每个因素的独立贡献，这一建议将提高对相互作用的理解 作为酒精敏感性调节因子的疼痛/酒精敏感性、性别和酗酒家族史之间的关系 止痛药。这些努力将为关于相关风险的进一步研究和临床/翻译工作提供信息 通过饮酒来自我治疗疼痛。关键是，这些因素对功能性 酒精镇痛的神经关联也将被确定，从而提高对酒精的机制的理解 止痛药。

Project Summary Pain is the most common reason that patients seek medical attention. Acute pain is an essential indicator of current or impending tissue damage. However, chronic pain is a maladaptive state with strong affective, biological, and psychological components. Chronic pain is extremely costly and has strong negative effects on sufferers’ quality of life. Existing treatments for chronic pain, including opioid analgesics, are relatively ineffective. Perhaps as a result of the lack of efficacious treatments, it has been recently reported that nearly 25% of individuals suffering from chronic oral and/or musculoskeletal pain self-medicate through the oral consumption of alcohol. Indeed, alcohol interacts with a wide range of relevant pharmacologic targets capable of modulating the experience of pain. However, the biological mechanisms underlying this intuitive interaction are not well established. This relationship is important to understand because alcohol analgesia may act as a potent negative reinforcer for alcohol intake, which, in turn, can have adverse health effects by increasing risk of developing an alcohol use disorder. Familial risk for alcoholism, along with sex and certain mood/personality factors, may act as critical modulators of individual sensitivity to alcohol analgesia. However, it is currently unclear whether this sensitivity is the result of neurobiological, and/or learned factors. By characterizing independent contributions of each of these factors, this proposal will improve understanding of the interplay between pain/alcohol sensitivity, sex, and family history of alcoholism as a modulator of sensitivity to alcohol analgesia. These efforts will inform further research and clinical/translational efforts regarding risk associated with self-medication of pain by consuming alcohol. Critically, the impact of these factors on the functional neural correlates of alcohol analgesia will also be determined, improving mechanistic understanding of alcohol analgesia.