Mechanisms of Triptan Action in Migraine and Pain

曲普坦治疗偏头痛和疼痛的作用机制

• 批准号: 6924528
• 负责人: ANDREW H AHN
• 金额: $ 16.14万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-15 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6924528
• 关键词: 3,4 methylenedioxymethamphetamine; amygdala; behavior test; dorsal raphe nucleus; in situ hybridization; laboratory rat; microinjections; migraine; neurons; pain; pathologic process; serotonin; serotonin receptor; sumatriptan

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、哲学博士是一位神经科医生，接受过分子和细胞生物学方面的培训。他的 K08 指导临床科学家职业发展奖将用于发展学术神经病学的职业生涯，其研究重点是了解偏头痛的基本机制。偏头痛是一种严重的神经系统疾病，在美国影响着超过 2700 万人，每年造成的工资和医疗损失高达 130 亿美元。研究计划：Ahn 博士将研究曲坦类药物的作用机制，曲坦类药物是用于治疗偏头痛的血清素受体亚型选择性激动剂。他根据初步发现计划进行一系列实验，即曲坦类受体（5HT1 D 型血清素受体）集中在杏仁核的中央和中央外侧核内，而杏仁核是大脑中在疼痛处理中发挥重要作用的区域。他将验证杏仁核内的这些末端起源于中缝背侧的假设，该结构也与疼痛调节相关，并且特别已知用于合成 5HTID 受体。然后，他将验证曲坦类药物通过激活杏仁核中的 5HTID 受体来影响疼痛处理的假设。为此，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诱发活动的直接电生理记录来跟踪这些结果。发展计划：Ahn博士已加入Allan I. Basbaum博士实验室。了解疼痛的基本机制，并学习动物模型中神经解剖学、生理学和疼痛行为的相关技术。此外，加州大学旧金山分校通过跨学科疼痛中心和完善的学术项目提供独特的培训环境。拟议的计划利用了巴斯鲍姆实验室在解剖学、行为和生理技术方面的专业知识，这些技术将培训安博士成为一名独立研究者。他还将借鉴医学博士、哲学博士 Howard L. Fields 长期的疼痛研究和生理学技能。作为共同发起人。安博士的职业目标是获得神经病学领域的终身学术职位，并通过独立的、研究者发起的资助，在他的研究实验室中研究偏头痛的基本机制。他所在机构衷心鼓励他申请临床医生研究员职位，重点关注未来几年的偏头痛研究。