Characterizing the effects of family history of alcoholism on alcohol analgesia

项目摘要 疼痛是患者寻求医疗护理的最常见原因。急性疼痛是一个重要指标， 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， 生理和心理因素。慢性疼痛是非常昂贵的，并有强烈的负面影响， 患者的生活质量。现有的慢性疼痛治疗方法，包括阿片类镇痛药，相对来说， 无效。也许是由于缺乏有效的治疗方法，最近有报道说， 25%患有慢性口腔和/或肌肉骨骼疼痛的人通过口腔 酒精消费。事实上，酒精与广泛的相关药理学靶点相互作用， 调节疼痛的体验。然而，这种直觉互动背后的生物机制 还没有很好地建立起来。这种关系是重要的理解，因为酒精镇痛可能作为一个 酒精摄入量的一种强有力的负向抑制剂，反过来，它会通过增加风险而对健康产生不利影响。 酒精使用障碍的可能性酗酒的家族风险，沿着性和某些情绪/个性 因素，可能作为个人敏感性的酒精镇痛的关键调制器。但目前 不清楚这种敏感性是否是神经生物学和/或学习因素的结果。通过表征 这些因素中的每一个的独立贡献，这一建议将提高对相互作用的理解 疼痛/酒精敏感性、性别和酒精中毒家族史作为酒精敏感性调节剂之间的关系 analgesia.这些工作将为进一步的研究和临床/转化工作提供信息， 通过饮酒来自我止痛关键是，这些因素对功能的影响 还将确定酒精镇痛的神经相关因素，提高对酒精机制的理解 analgesia.

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.