Sensitization in Trigeminal Neurons: A Role in Migraine?

三叉神经元的敏化：在偏头痛中的作用？

基本信息

批准号：
7424934
负责人：
JOYCE H HURLEY
金额：
$ 16.56万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
依托单位国家：
美国
项目类别：
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/7424934
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

项目摘要

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-Type钙通道在偏头痛中的作用。在家族性偏瘫偏头痛和“常见”偏头痛患者中，最近发现P/Q-Type钙通道中的遗传突变令人惊讶，尤其是鉴于大多数偏头痛治疗是5-羟色胺受体受体激动剂。偏头痛的病理生理学中有缺陷的钙通道和5-羟色胺受体之间存在什么关系。三叉神经元是偏头痛疼痛产生和传播的重要解剖部位。三叉神经元表达多种类型的钙通道，包括P/Q-Type钙通道和5-羟色胺受体，但其功能尚未得到彻底研究。我们将使用斑板钳电生理学来确定单个三叉神经元的P/Q-Type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。我们已经表明，5-羟色胺1型激动剂抑制三叉神经元中的总钙电流幅度并抑制CGRP释放。我们计划鉴定介导这种作用的5-羟色胺受体以及抑制作用。这些研究将促进我们对三叉神经元中正常钙通道功能的知识，并将提供知识的基础，以检验三叉神经元中有缺陷的钙通道在偏头痛的病理生理学中很重要。