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Mechanisms of Triptan Action in Migraine and Pain

曲普坦治疗偏头痛和疼痛的作用机制

基本信息

批准号：
7869559
负责人：
ANDREW H AHN
金额：
$ 5.4万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-07-15 至 2010-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7869559
关键词：
Acute Pain Affect Afferent Neurons Agonist American Amygdaloid structure Animal Model Animals Antibodies Area Behavior Behavioral Behavioral Model Brain Brain region Caring Cell Nucleus Cellular biology Chemical Stimulation Clinical Development Doctor of Medicine Doctor of Philosophy Dorsal Dura Mater Electric Stimulation Environment Experimental Designs Functional disorder Funding Goals Head In Situ Hybridization Inflammation Inflammatory Injection of therapeutic agent Injury Institution K-Series Research Career Programs Label Laboratories Laboratory Research Lead Learning Measures Mediating Medical Mentors Messenger RNA Methods Microinjections Migraine Modeling Molecular Nerve Neuroanatomy Neurobiology Neurologic Neurologist Neurology Neurons Nociception Nociceptors Pain Pain Clinics Pain Research Peripheral Pharmaceutical Preparations Phenotype Physiological Physiology Positioning Attribute Process Prosencephalon Rattus Receptor Activation Recurrence Research Research Personnel Rest Role Scientist Series Serotonin Spinal Cord Structure Sumatriptan Techniques Testing Training Trigeminal Nuclei United States Wages aversive conditioning base career central sensitization cost ecstasy extracellular follow-up immunoreactivity insight interest neurochemistry novel pain behavior prevent programs receptor research study serotonin receptor serotonin transporter skills triptans

项目摘要

DESCRIPTION (provided by applicant): Andrew H. Ahn, M.D., Ph.D. is a neurologist with prior training in molecular and cell biology. His K08 Mentored Clinical Scientist Career Development Award will be used to develop a career in academic neurology with a research focus on understanding the basic mechanisms of migraine. Migraine is a significant neurological condition that affects over 27 million people in the United States with an annual cost of up to $13 billion in lost wages and medical care. Research Plan: Dr. Ahn will study the mechanism of action of the triptans, serotonin receptor subtype-selective agonists used in the treatment of migraine headache. He plans a series of experiments based on his preliminary findings that a triptan receptor, serotonin receptor subtype 5HT1 D, is concentrated within the central and centrolateral nuclei of the amygdala, regions of the brain with prominent roles in pain processing. He will test the hypothesis that these terminals within the amygdala originate in the dorsal raphe, a structure also relevant to pain modulation and specifically known to synthesize 5HTID receptor. He will then test the hypothesis that triptans affect pain processing through their activation of 5HTID receptors in the amygdala. To do this, he will determine the ability of triptans to interfere with a behavioral model of learned pain-aversive behavior and will follow up on these results with direct electrophysiological recordings of evoked activity in the trigeminal nucleus. Developmental Plan: Dr. Ahn has joined the laboratory of Allan I. Basbaum, Ph.D. to gain an understanding of the basic mechanisms of pain, as well as to learn the relevant techniques of neuroanatomy, physiology and pain behavior in animal models. In addition, UCSF provides a unique training environment through an interdisciplinary pain center with a well-developed academic program. The proposed plan draws upon the expertise of the Basbaum Laboratory in the anatomical, behavioral and physiological techniques that will train Dr. Ahn's to become an independent investigator. He will also draw upon the longstanding pain research and physiology skills of Howard L. Fields, M.D., Ph.D. as a co-sponsor. Dr. Ahn's professional goals are to obtain a tenure-track academic position in neurology, and to investigate the basic mechanisms of migraine in his research laboratory through independent, investigator-initiated funding. He has the wholehearted encouragement of his institution in applying for a clinician-investigator position with a focus on migraine research in the coming years.

描述（由申请人提供）：Andrew H. Ahn，医学博士，博士是一名神经科医生，曾接受过分子和细胞生物学方面的培训。他的K 08指导临床科学家职业发展奖将用于发展学术神经学的职业生涯，研究重点是了解偏头痛的基本机制。偏头痛是一种重要的神经系统疾病，影响美国超过2700万人，每年损失的工资和医疗费用高达130亿美元。研究计划：安博士将研究曲坦类药物的作用机制，曲坦类药物是一种用于治疗偏头痛的5-羟色胺受体亚型选择性激动剂。他计划根据他的初步发现进行一系列实验，这些发现是一种曲坦受体，即5-羟色胺受体亚型5 HT 1 D，集中在杏仁核的中央和中央外侧核，这是大脑中在疼痛处理中起重要作用的区域。他将测试杏仁核内的这些终端起源于中缝背核的假设，中缝背核也与疼痛调制有关，并且特别已知合成5 HTID受体。然后，他将测试曲坦类药物通过激活杏仁核中的5 HTID受体来影响疼痛处理的假设。为了做到这一点，他将确定曲坦类药物干扰习得性疼痛厌恶行为的行为模型的能力，并将通过三叉神经核中诱发活动的直接电生理记录来跟踪这些结果。发展计划：安博士加入了艾伦I的实验室。Basbaum博士了解疼痛的基本机制，以及学习神经解剖学、生理学和动物模型疼痛行为的相关技术。此外，UCSF通过跨学科的疼痛中心提供了一个独特的培训环境，并提供了完善的学术课程。拟议的计划借鉴了Basbaum实验室在解剖学、行为学和生理学技术方面的专业知识，这些技术将训练Ahn博士成为一名独立的调查员。他还将借鉴霍华德L.菲尔兹医学博士博士作为一个共同赞助商。Ahn博士的职业目标是获得神经病学的终身学术职位，并通过独立的，由医生发起的资金在他的研究实验室中调查偏头痛的基本机制。他得到了所在机构的大力鼓励，申请了一个临床研究员的职位，在未来几年里专注于偏头痛的研究。