Mechanisms of Alcohol Hangover Headache

酒精宿醉头痛的机制

基本信息

批准号：
8420542
负责人：
DAN LEVY
金额：
$ 19.22万
依托单位：
BETH ISRAEL DEACONESS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-02-10 至 2015-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8420542
关键词：
Accidents Acetaldehyde Acetates Acute Address Adolescence Affect Age Alcohol abuse Alcohol consumption Alcohol dehydrogenase Alcohol dependence Alcoholic Beverages Alcoholic Intoxication Alcoholism Alcohols Animal Model Basic Science Biological Cardiovascular system Chemicals Clinical Research Cyanamide Data Development Disulfiram Dose Enhancers Ethanol Ethanol Metabolism Etiology Fatigue Formates Formic Acids Frequencies Future Headache Health Hour Human Impairment Individual Ingestion Intake Intoxication Investigation Knowledge Link Mechanics Mediating Meningeal Methanol Molecular Nausea Neurocognitive Neurons Nociceptors Pattern Peripheral Physiological Plasma Play Population Predisposition Process Productivity Rattus Relative (related person)Reporting Residual state Risk Role Symptoms Thirst Throbbing Headaches Time Time Factors Time Study acetaldehyde dehydrogenase alcohol effect alcohol related problem alcohol response alcohol use disorder drinking fomepizole hangover hangover from alcohol in vivo inhibitor/antagonist men middle age mortality neurobiological mechanism neurophysiology pre-clinical problem drinker relating to nervous system research study response socioeconomics theories

项目摘要

DESCRIPTION (provided by applicant): Acute excessive consumption of alcoholic beverages leads, after a delay, to a post-intoxication period known as the "hangover", which consists of throbbing headache as well as numerous other unpleasant physical symptoms. Hangover has many socioeconomic consequences, including reduced productivity and increased accident risk. Hangover headache proneness has been associated with increased risk for future development of alcohol use disorders. How hangover headache plays a role in the etiology of alcohol use disorders as well as other alcohol-related problems remains an open question, largely because the factors and neuronal mechanisms that mediate the hangover symptoms, including the headache are poorly understood. This lack of knowledge can be attributed, in part to the paucity of clinical studies and the almost complete lack of basic research on the physiological and neurophysiological processes underlying the phenomenon. We have previously established a unique animal model for studying the activity and mechanosensitivity of meningeal nociceptors, the peripheral neuronal population that has been most directly implicated in the genesis of headache. We now propose to use this animal model to investigate for the first time the factors that play a role in mediating the hangover headache, one of the most common symptoms of the hangover state. Using in vivo single unit recordings of meningeal nociceptors in anesthetized rats, we propose to start this line of investigation by addressing the identity of the alcohol-related substances as well as the neural processes that might potentially contribute to the hangover headache. Specific aim 1 will examine time-course and dose- related effects of acute ethanol administration on the activity and mechanosensitivity of meningeal nociceptors. Specific Aim 2 will determine the relative contribution of ethanol's first metabolite acetaldehyde in mediating meningeal nociceptor activation and sensitization following administration of intoxicating doses of ethanol. Specific Aim 3 will examine whether methanol, one of the major toxic congeners found in alcoholic beverages or its metabolites formate and formic acid increase the activity and mechanosensitivity of meningeal nociceptors and further determine whether methanol can enhance or prolong the activation and sensitization of meningeal nociceptors associated with acute ethanol intoxication. These experiments are the first methodological step in the study of the neurobiological mechanisms underlying a major hangover symptom, the headache. Data from this exploratory project will begin to fill the gaps in our knowledge regarding the factors and processes the may contribute to the hangover headache and provide much needed data to generate further testable hypotheses on the origin of the headache and potentially other hangover symptoms. Data will be instrumental in future studies that address the question of how the degree of sensitivity to hangover is related to differences in the propensity of developing alcoholism and potentially other hangover- related health problems.

描述（由申请人提供）：急性过度食用酒精饮料后，延迟后，将其延迟到后期毒性期，称为“宿醉”，其中包括头痛以及许多其他不愉快的身体症状。宿醉具有许多社会经济后果，包括降低生产率和增加事故风险。宿醉的头痛pre骨与饮酒障碍未来发展的风险增加有关。宿醉的头痛如何在酒精使用障碍的病因以及其他与酒精相关的问题中发挥作用，这主要是一个悬而未决的问题，这主要是因为介导宿醉症状的因素和神经元机制，包括头痛在内的知识很少。缺乏知识可以归因于临床研究的匮乏以及几乎完全缺乏有关该现象背后的生理和神经生理过程的基础研究。我们以前已经建立了一种独特的动物模型，用于研究脑膜伤害感受器的活性和机械敏感性，脑膜伤害感受器是最直接与头痛起源有关的周围神经元种群。现在，我们建议使用该动物模型首次调查这些因素在介导宿醉头痛中起作用，这是宿醉状态的最常见症状之一。我们建议在麻醉大鼠中使用脑膜伤害感受器的体内单位记录，我们建议通过解决酒精相关物质的身份以及可能有助于宿醉头痛的神经过程来开始这种研究。特定的目标1将检查急性乙醇给药对脑膜伤害感受器的活性和机械效率的时间课程和剂量相关的影响。具体的目标2将确定乙醇在介导脑膜伤害感受器激活和敏化剂量后，乙醇的第一个代谢产物乙醛在陶醉剂量的乙醇后的相对贡献。具体目的3将检查甲醇是在酒精饮料或其代谢物甲酸甲酸甲酸甲酸甲酸甲酸甲酸甲酸甲酸甲酸甲酸甲醇和甲酸中是否会增加脑膜伤害感受器的活性和机械敏感性，并且进一步确定甲醇是否可以增强或延长与与急性乙醇相关的脑膜伤害感受器的激活和敏感性。这些实验是研究主要宿醉症状的神经生物学机制的第一步，即头痛。该探索性项目的数据将开始填补我们有关可能导致宿醉头痛的因素和过程的知识的空白，并提供急需的数据，以产生有关头痛起源以及潜在的其他宿醉症状的进一步可检验的假设。数据将在未来的研究中发挥作用，该研究解决了对宿醉的敏感程度与发展酗酒倾向以及潜在的其他宿醉与健康问题的差异有关的问题。