Mechanisms of Triptan Action in Migraine and Pain

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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.