Rodent model of alcohol related hyperalgesia

酒精相关痛觉过敏啮齿动物模型

• 批准号: 10189448
• 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 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10189448
• 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; Pathology; Patients; 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; chronic pain patient; chronic painful condition; designer receptors exclusively activated by designer drugs; drinking; drinking behavior; experimental study; hypothalamic-pituitary-adrenal axis; male; negative affect; neuromechanism; novel; pain perception; pain relief; pain sensitivity; 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 超过一亿美国人患有慢性疼痛，超过一千万的美国人遭受 酗酒或依赖。慢性疼痛与酒精之间存在双向关系 依赖。那是饮酒是慢性疼痛严重程度的主要预测指标，患有 慢性疼痛状况更有可能使用酒精缓解疼痛。不幸的是，一种机械 缺乏了解与酒精相关的疼痛敏感性的理解。我们的研究已经确定了增加的疼痛 从自愿性酒精自我给药中退出时，小鼠的敏感性。在这些中消费酒精 小鼠逆转了戒酒产生的机械性超敏反应。疼痛的敏感性增加 进行戒断的小鼠与酒精依赖性患者的疼痛增加一致。另外，我们 发现在控制“旁观者”小鼠中，疼痛敏感性提高了与接受的小鼠相同房间的疼痛敏感性 戒酒。来自小鼠的痛觉过敏的社会转移，经过戒断向旁观者小鼠 涉及嗅觉提示。这种痛苦的社会转移可能会影响“共同依赖”的家庭成员 酒精患者。免疫组织化学分析表明背侧下丘脑的差异激活， 这些动物中的前扣带回和前岛皮层。我们假设确定的大脑区域 与酒精戒断诱导的痛觉过敏和社会转移的痛觉过敏有关。 该提议的目的是解决这一假设，并进一步描述酒精现象 提款和社会转移引起的痛觉过敏。这个目标将在三个具体目标中实现：目标1 将进一步表征戒酒和旁观者小鼠中痛觉过敏现象 检查观察到的热痛觉过敏是否在女性旁观者小鼠中夸大了 负面情感状态，焦虑或压力反应或与抑郁症行为共存。 AIM 2意志 测试酒精诱导的背侧下丘脑中神经元种群的激活是否需要 足以调节小鼠疼痛敏感性和饮酒行为。 AIM 3将测试是否 戒酒和社交转移引起的前扣带回和/或岛神经元的激活是 必要且足以调节疼痛敏感性。