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

酒精与疼痛的联系：机制和遗传/心理相关性

• 批准号: 9082330
• 负责人: JOSEPH W. DITRE
• 金额: $ 33.37万
• 依托单位: SYRACUSE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9082330
• 关键词: Absence of pain sensation; Acute; Affect; Affective; Alcohol Phenotype; Alcohol consumption; Alcohol dependence; Alcoholic beverage heavy drinker; Alcoholism; Alcohols; Analgesics; Anxiety; Attention; Biological; Candidate Disease Gene; Capsaicin; Clinical Trials; Cognitive; Communities; Complex; Consumption; Data; Development; Dose; Ensure; Etiology; Evaluation; Expectancy; Family history of; Future; Gender; Genes; Genetic; Genetic Polymorphism; Genome; Goals; Heating; Heavy Drinking; Human; Individual; Investments; Literature; Measures; Mediating; Mediator of activation protein; Methods; Modeling; Motivation; Outcome; Outcome Study; Pain; Participant; Pathway interactions; Patient Self-Report; Placebo Control; Placebo Effect; Placebos; Process; Randomized; Recruitment Activity; Reporting; Research; Rest; Schedule; Staging; Stimulus; Taste Perception; Testing; Translating; Translational Research; United States National Institutes of Health; Variant; Visit; Woman; Work; alcohol effect; alcohol expectancy; alcohol use disorder; base; biopsychosocial; catalyst; chronic pain; clinical application; clinical practice; drinking; expectation; experience; genetic variant; genome-wide; innovation; men; negative affect; novel; pain inhibition; psychologic; public health relevance; response; theories

 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.

 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，值得对其病因和治疗进行现有的研究投资。此外，这些条件之间的显着共同发生的证据提供了一个机会，以检查酒精疼痛连接的机制，可能会告知新的治疗方法的发展。与NIH PA-15-026（疼痛和酒精依赖的机制研究）一致，拟议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。主要研究目的如下：（1）在人类急性酒精镇痛中进行药理学和预期效应的首次测试;（2）进行疼痛作为饮酒冲动和随意饮酒的近端前因的首次测试，并测试急性镇痛效应是否预测疼痛诱导的饮酒冲动/消费;（3）测试研究结果与疼痛-酒精过程中涉及的候选遗传多态性之间的关联;（4）对性别和疼痛相关认知情感因素进行探索性分析，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（中等剂量vs.低剂量vs.安慰剂vs.对照）和静态/动态疼痛反应的前/后评估（研究访视1），以及辣椒素/热痛诱导（vs.无疼痛诱导），然后评估饮酒欲望和随意饮酒（研究访视2）。通过采用一种新的实验范式，研究结果将提供内部有效的数据，为将这些发现转化为临床应用提供明确和直接的影响。我们期望这项工作将促进未来的研究，并通过建立一个实验平台来告知临床实践，该平台允许证明因果效应，在进行昂贵的临床试验之前评估治疗成分，并确定重要的基于理论的生物心理社会机制，这些机制可以为患有共同发生的疼痛和酒精使用障碍的个体提供新的综合治疗方法。