Mechanisms of Triptan Action in Migraine and Pain

简介(申请人提供)：Andrew H.Ahn，M.D.，Ph.D.是一名神经学家，曾受过分子和细胞生物学方面的培训。他的K08临床科学家导师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。偏头痛是一种严重的神经疾病，在美国有2700多万人受到影响，每年在工资和医疗方面的损失高达130亿美元。研究计划：安博士将研究Triptans的作用机制，Triptans是用于治疗偏头痛的5-羟色胺受体亚型选择性激动剂。根据他的初步发现，他计划进行一系列实验，根据他的初步发现，Triptan受体5HT1D亚型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发挥重要作用的区域。他将测试杏仁核内这些终末起源于中缝背侧的假设，中缝背侧结构也与痛觉调制有关，并专门合成5HTID受体。然后，他将验证这样一个假设，即雷公藤通过激活杏仁核中的5HTID受体来影响疼痛处理。为了做到这一点，他将确定Triptans干扰获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进这些结果。发展计划：安博士已加入Allan I.Basbaum博士的实验室，以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一个跨学科的疼痛中心提供独特的培训环境，该中心拥有完善的学术计划。拟议的计划利用了巴斯鲍姆实验室在解剖学、行为学和生理学技术方面的专业知识，这些技术将培训安博士成为一名独立的研究员。他还将利用霍华德·L·菲尔兹医学博士的长期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在神经学领域获得终身教职，并通过研究人员发起的独立资助，在他的研究实验室中研究偏头痛的基本机制。他得到了他所在机构的衷心鼓励，申请了一个临床医生兼研究员的职位，在未来几年专注于偏头痛研究。

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.