The Alcohol-Pain Connection: Mechanisms and Genetic/Psychological Correlates

 描述(由申请人提供)：大量饮酒和慢性疼痛的社会影响是巨大的，需要对其病因和治疗进行现有的研究投资。此外，这些情况之间显著共存的证据为研究酒精与疼痛联系的机制提供了机会，这可能会为开发新的治疗方法提供信息。与NIH PA-15-026(疼痛和酒精依赖的机制研究)一致，拟议的研究的目标是在一个总体模型中检查疼痛和酒精之间的几个复杂的和潜在的双向关系，这在人类实验范式中从未尝试过。主要研究目标如下：(1)首次测试人类急性酒精镇痛的药理效应和预期效应；(2)首次测试疼痛作为饮酒冲动和随意饮酒的近端前驱因素，并测试急性止痛效应是否可以预测疼痛诱导的酒精冲动/消费；(3)测试研究结果与参与疼痛-酒精过程的候选基因多态之间的关联；以及(4)探索性分析性别和疼痛相关认知情感因素作为这些结果的调节因素。参与者将包括从当地社区招募的280名中度至重度饮酒者。实验方法将包括酒精给药(中剂量与低剂量与安慰剂与对照组相比)和静态/动态疼痛反应的事前/事后评估(研究访问1)，以及辣椒素/热疼痛诱导(与不诱导疼痛)，然后评估饮酒冲动和即兴饮酒(研究访问2)。通过采用新的实验范式，研究结果将为将这些发现转化为临床应用提供明确和直接的内部有效数据。我们期望这项工作将通过建立一个实验平台来催化未来的研究并为临床实践提供信息，该平台允许在进行昂贵的临床试验之前展示因果效应、评估治疗成分，并确定重要的基于理论的生物心理社会机制，这些机制可以为开发针对共生疼痛和酒精使用障碍的新型综合治疗方法提供信息。

 DESCRIPTION (provided by applicant): The societal impact of heavy alcohol consumption and chronic pain is substantial and warrants the existing research investment into their etiology and treatment. Moreover, evidence of significant co-occurrence between these conditions offers an opportunity to examine mechanisms in the alcohol-pain connection that may inform the development of novel treatments. Consistent with NIH PA-15-026 (Mechanistic Studies of Pain and Alcohol Dependence), the goal of the proposed study is to examine several complex and potentially bidirectional relations between pain and alcohol in one overarching model, which has never been attempted in a human experimental paradigm. The primary study aims are as follows: (1) to conduct the first test of both pharmacological and expectancy effects in acute alcohol analgesia among humans; (2) to conduct the first test of pain as a proximal antecedent of urge to drink and ad lib alcohol consumption, and to test whether acute analgesic effects predict pain-induced alcohol urge/consumption; (3) to test associations between study outcomes and candidate genetic polymorphisms that have been implicated in pain-alcohol processes; and (4) to conduct exploratory analyses of gender and pain relevant cognitive-affective factors as moderators of these outcomes. Participants will include 280 moderate-to-heavy drinkers recruited from the local community. Experimental methods will include alcohol administration (moderate dose vs. low dose vs. placebo vs. control) and pre/post assessment of static/dynamic pain responses (study visit 1), and capsaicin/heat pain induction (vs. no pain induction) followed by assessment of urge to drink and ad lib alcohol consumption (study visit 2). By employing a novel experimental paradigm, the study results will provide internally valid data with clear and direct implications for translating these findings to clinical applications. Itis our expectation that this work will catalyze future research and inform clinical practice by establishing an experimental platform that allows for the demonstration of causal effects, the evaluation of treatment components prior to conducting costly clinical trials, and the identification of important theory-based biopsychosocial mechanisms that can inform the development of novel integrated treatments for individuals with co-occurring pain and alcohol use disorders.