Sensitization in Trigeminal Neurons: A Role in Migraine?

三叉神经元的敏化：在偏头痛中的作用？

• 批准号: 7235987
• 负责人: JOYCE H HURLEY
• 金额: $ 16.61万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7235987
• 关键词: Acute; Agonist; Attenuated; Blood Vessels; Calcitonin Gene-Related Peptide; Calcium; Calcium Channel; Cells; Cerebrum; Characteristics; Common Migraine; Condition; Data; Disease; Electrophysiology (science); Etiology; Familial Hemiplegic Migraine; Foundations; Functional disorder; G-Protein-Coupled Receptors; Gene Mutation; Goals; Individual; Inflammatory; Knowledge; Label; Light; Mediating; Mediator of activation protein; Migraine; Mutation; Nerve; Nerve Endings; Neurons; Neurotransmitters; Pain; Patients; Pharmaceutical Preparations; Physiological; Play; Population; Production; Q-Type Calcium Channels; Regulation; Relative (related person); Research Personnel; Role; Serotonin; Serotonin Agonists; Site; Subgroup; Symptoms; System; Techniques; Testing; Trigeminal System; Trigeminal nerve structure; Vasodilator Agents; Work; base; immunocytochemistry; insight; neurotransmitter release; patch clamp; programs; receptor expression; research study; response; serotonin receptor; transmission process

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.

描述（由申请人提供）：该项目的长期目标是了解 P/Q 型钙通道在偏头痛中的作用。最近在家族性偏瘫偏头痛和“常见”偏头痛患者中发现 P/Q 型钙通道基因突变令人惊讶，尤其是考虑到大多数偏头痛治疗都是血清素受体激动剂。在偏头痛的病理生理学中，缺陷的钙通道和血清素受体之间存在什么关系（如果有的话）尚不清楚。三叉神经元是偏头痛疼痛产生和传递的重要解剖部位。三叉神经元表达多种类型的钙通道，包括 P/Q 型钙通道和血清素受体，但其功能尚未得到彻底研究。我们将使用膜片钳电生理学来确定单个三叉神经元上 P/Q 型通道的相对丰度、它们在神经元亚群中的分布以及它们在神经递质释放中的作用。我们已经证明 1 型 5-羟色胺激动剂可抑制三叉神经元中的总钙电流振幅并抑制 CGRP 释放。我们计划鉴定介导这种作用的血清素受体以及抑制机制。这些研究将增进我们对三叉神经元正常钙通道功能的认识，并为检验三叉神经元钙通道缺陷在偏头痛病理生理学中重要这一假设提供基础知识。