Mechanisms of Triptan Action in Migraine and Pain

简介（由申请人提供）：Andrew H. Ahn, m.d.，博士，神经学家，在分子和细胞生物学方面受过训练。他的K08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。偏头痛是一种严重的神经系统疾病，在美国影响着2700多万人，每年在工资和医疗保健方面的损失高达130亿美元。研究计划：Ahn博士将研究用于治疗偏头痛的血清素受体亚型选择性激动剂曲坦类药物的作用机制。他计划在初步发现的基础上进行一系列实验，发现曲坦类受体（5 -羟色胺受体亚型5HT1 D）集中在杏仁核的中央和中央外侧核中，这两个区域在疼痛处理中起着重要作用。他将验证杏仁核内的这些终端起源于中缝背的假设，中缝背是一个与疼痛调节有关的结构，特别是已知的合成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对习得性疼痛厌恶行为行为模型的干扰能力，并将对这些结果进行三叉神经核诱发活动的直接电生理记录。发展计划：Ahn博士加入了Allan I. Basbaum博士的实验室，以了解疼痛的基本机制，以及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还通过一个跨学科的疼痛中心提供了一个独特的培训环境，该中心拥有完善的学术项目。拟议中的计划借鉴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，这些技术将训练安博士成为一名独立的研究者。他还将借鉴霍华德L.菲尔兹的长期疼痛研究和生理学技能，医学博士，博士作为共同发起人。Ahn博士的职业目标是获得神经学领域的终身学术职位，并通过独立的研究者发起的资助，在他的研究实验室研究偏头痛的基本机制。他得到了他所在机构的全力鼓励，申请在未来几年专注于偏头痛研究的临床研究员职位。

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.