Rodent model of alcohol related hyperalgesia

酒精相关痛觉过敏啮齿动物模型

• 批准号: 9380282
• 负责人: Mary Magdalen Heinricher
• 金额: $ 34.65万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9380282
• 关键词: Acute; Address; Affect; Agreement; Alcohol abuse; Alcohol consumption; Alcohol dependence; Alcohol withdrawal syndrome; Alcohols; American; Animals; Anterior; Anxiety; Area; Behavior; Behavior Therapy; Brain region; Chemicals; Cholecystokinin; Chronic; Cues; Empathy; Exhibits; FOS gene; Family member; Female; Glutamates; Goals; Heavy Drinking; House mice; Hyperalgesia; Hypersensitivity; Hypothalamic structure; Insula of Reil; Intervention Studies; Laboratories; Link; Measures; Mechanics; Mediating; Mental Depression; Mus; Mutant Strains Mice; Neurons; Neuropeptides; Neurosciences; Nociception; Pain; Pain Disorder; Pathology; Patients; Perception; Pharmacotherapy; Play; Population; Procedures; Regulation; Reporting; Research; Rodent Model; Role; Self Administration; Severities; Spouses; Testing; Thermal Hyperalgesias; Time; Withdrawal; alcohol abuse therapy; biological adaptation to stress; chronic pain; designer receptors exclusively activated by designer drugs; drinking; drinking behavior; experimental study; hypothalamic-pituitary-adrenal axis; male; negative affect; neuromechanism; novel; prairie vole; preclinical study; problem drinker; social; therapy development; transcription factor; treatment trial

Project Summary Over a hundred million of Americans suffer from chronic pain and over ten million of Americans suffer from alcohol abuse or dependence. There is a bidirectional relationship between chronic pain and alcohol dependence. Thus, alcohol dependence is a major predictor of severity of chronic pain, and people with chronic pain conditions are more likely to use alcohol for pain relief. Unfortunately, a mechanistic understanding of alcohol-related pain sensitivity is lacking. Our studies have identified increased pain sensitivity in mice during withdrawal from voluntary alcohol self-administration. Consumption of alcohol in these mice reversed mechanical hypersensitivity produced by alcohol withdrawal. The increased pain sensitivity in mice undergoing withdrawal is consistent with increased pain in alcohol-dependent patients. In addition, we found increased pain sensitivity in control “bystander” mice housed in the same room as mice undergoing alcohol withdrawal. The social transfer of hyperalgesia from mice undergoing withdrawal to the bystander mice involved olfactory cues. Such social transfer of hyperalgesia could affect "co-dependent" family members of alcoholic patients. Immunohistochemical analysis revealed differential activation of dorsomedial hypothalamus, anterior cingulate and anterior insular cortex in these animals. We hypothesize that the identified brain regions are differentially involved in alcohol withdrawal-induced hyperalgesia and socially-transferred hyperalgesia. The goal of this proposal is to address this hypothesis and further characterize the phenomena of alcohol withdrawal- and social transfer-induced hyperalgesia. This goal will be achieved in three Specific Aims: Aim 1 will further characterize the phenomenon of hyperalgesia in alcohol withdrawing and bystander mice by examining whether the observed thermal hyperalgesia is exaggerated in female bystander mice, involves negative affective states, anxiety or stress responses, or coexists with depression-like behaviors. Aim 2 will test whether alcohol-induced activation of neuronal populations within dorsomedial hypothalamus is necessary and sufficient for regulation of pain sensitivity and alcohol drinking behavior in mice. Aim 3 will test whether alcohol withdrawal and social transfer-induced activation of neurons of anterior cingulate and/or insula are necessary and sufficient for regulation of pain sensitivity.

项目摘要 超过1亿的美国人患有慢性疼痛，超过1000万的美国人患有 酗酒或依赖。慢性疼痛与酒精之间存在双向关系 依赖。因此，酒精依赖是慢性疼痛严重性的主要预测因素，而患有酒精依赖的人 慢性疼痛情况下更有可能使用酒精来缓解疼痛。不幸的是，一个机械主义者 对酒精相关的疼痛敏感性缺乏了解。我们的研究发现疼痛增加 自愿戒酒过程中小鼠的敏感性。这些饮料中的酒精消耗量 小鼠逆转了酒精戒断所产生的机械过敏。增加的疼痛敏感度 戒断的小鼠与酒精依赖患者疼痛增加是一致的。此外，我们 研究发现，与实验小鼠同处一室的对照组“旁观者”小鼠的疼痛敏感度增加。 戒酒。痛觉过敏从戒断小鼠到旁观者的社会传递 涉及到嗅觉线索。这种痛觉过敏的社会转移可能会影响到相互依赖的家庭成员 酗酒的病人。免疫组织化学分析显示背内侧下丘脑有不同程度的激活， 这些动物的前扣带回和前岛叶皮质。我们假设识别出的大脑区域 不同程度地参与酒精戒断引起的痛觉过敏和社会传递性痛觉过敏。 这项提议的目标是解决这一假说，并进一步描述酒精现象 戒断和社会转移导致的痛觉过敏。这一目标将通过三个具体目标实现：目标1 将进一步表征酒精戒断和旁观者小鼠的痛觉过敏现象 检查观察到的热痛觉过敏在雌性旁观者小鼠中是否被夸大，包括 消极的情感状态、焦虑或压力反应，或与类似抑郁的行为共存。目标2将 测试酒精是否有必要激活下丘脑背内侧的神经元群 并足以调节小鼠的疼痛敏感性和饮酒行为。AIM 3将测试 酒精戒断和社会转移诱导的前扣带回和/或岛叶神经元的激活 对疼痛敏感性的调节是必要的和充分的。