Rodent model of alcohol related hyperalgesia

酒精相关痛觉过敏啮齿动物模型

基本信息

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
项目类别：
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

项目摘要

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.

项目概要超过一亿美国人患有慢性疼痛，超过一千万美国人患有慢性疼痛酒精滥用或依赖之间存在双向关系。因此，酒精依赖是慢性疼痛严重程度的主要预测因素。不幸的是，慢性疼痛更有可能使用酒精来缓解疼痛。我们缺乏对酒精相关疼痛敏感性的了解。我们的研究发现疼痛会增加。小鼠在退出自愿饮酒期间的敏感性。小鼠逆转了戒酒引起的机械过敏，增加了疼痛敏感性。小鼠戒断反应与酒精依赖患者的疼痛增加一致。发现与接受治疗的小鼠住在同一房间的对照“旁观者”小鼠的疼痛敏感性增加酒精戒断小鼠的痛觉过敏的社会转移到旁观者小鼠。涉及嗅觉线索的这种痛觉过敏的社会转移可能会影响“共同依赖”的家庭成员。免疫组织化学分析揭示了下丘脑背内侧的差异激活，我们捕获了这些动物的前扣带皮层和前岛叶皮质。不同程度地参与酒精戒断引起的痛觉过敏和社会转移性痛觉过敏。该提案的目标是解决这一假设并进一步描述酒精现象戒断和社会转移引起的痛觉过敏将通过三个具体目标来实现：目标 1。将进一步表征酒精戒断小鼠和旁观者小鼠的痛觉过敏现象检查雌性旁观者小鼠中观察到的热痛觉过敏是否被夸大，涉及目标 2 会出现负面情绪状态、焦虑或压力反应，或与抑郁样行为共存。测试酒精诱导下丘脑背内侧神经群的激活是否必要并足以调节小鼠的疼痛敏感性和饮酒行为，目的 3 将测试是否有效。酒精戒断和社会转移引起的前扣带回和/或岛叶神经元的激活是对于调节疼痛敏感性是必要且充分的。