Sensitization in Trigeminal Neurons: A Role in Migraine?

Indiana Univ-Purdue Univ At Indianapolis, Indianapolis IN

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Abstract

DESCRIPTION (provided by applicant): The long-term goals of this project are to understand the role of the P/Q-type calcium channel in migraine. The recent discovery of genetic mutations in P/Q-type calcium channels in patients with Familial Hemiplegic Migraine and "common" migraine was surprising especially in light of the fact that most migraine treatments are serotonin receptor agonists. What relationship, if any, exists between defective calcium channels and serotonin receptors in the pathophysiology of migraine is unclear. Trigeminal neurons are an important anatomical site for pain production and transmission in migraine. Trigeminal neurons express multiple types of calcium channels, including the P/Q-type calcium channel, and serotonin receptors but their functions have not been thoroughly investigated. We will use patch-clamp electrophysiology to determine the relative abundance of P/Q-type channels on individual trigeminal neurons, their distribution within sub-populations of neurons and their role in neurotransmitter release. We have shown that serotonin Type 1 agonists inhibit total calcium current amplitude in trigeminal neurons and inhibit CGRP release. We plan to identify the serotonin receptor(s) mediating this effect, as well as the mechanism of inhibition. These studies will advance our knowledge about normal calcium channel function in trigeminal neurons and will provide a foundation of knowledge with which to test the hypothesis that defective calcium channels in trigeminal neurons are important in the pathophysiology of migraine.