Transient receptor potential melastatin 8 is required for nitroglycerin- and calcitonin gene-related peptide-induced migraine-like pain behaviors in mice.
Transient receptor potential melastatin 8 is required for nitroglycerin- and calcitonin gene-related peptide-induced migraine-like pain behaviors in mice.
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DOI：
10.1097/j.pain.0000000000002635
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发表时间：
2022-12-01
期刊：
影响因子：
7.4
通讯作者：
中科院分区：
文献类型：
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偏头痛是一种复杂的神经血管疾病，是导致残疾和生活质量下降的主要原因之一。即使有如此高的社会影响，我们对导致偏头痛的细胞和分子机制的理解仍然有限。为了解决这种复杂的疾病，几个小组已经进行了全基因组关联研究，以阐明偏头痛易感基因，其中许多识别瞬时受体电位melastatin 8（TRPM 8），一种在支配三叉神经血管系统的外周传入神经中表达的冷敏感阳离子通道，以及与损伤和疾病相关的寒冷和冷痛的主要介质。有趣的是，这些与偏头痛相关的单核苷酸多态性位于TRPM8的非编码区，与降低偏头痛风险相关的单核苷酸多态性表现出较低的TRPM8表达和较低的冷敏感性。尽管如此，由于TRPM8在偏头痛中的作用尚未确定，我们试图利用小鼠遗传学和TRPM8拮抗作用来解决我们知识中的这一差距，以确定TRPM8通道或神经元是否是诱导型偏头痛模型中偏头痛样疼痛（机械性异常性疼痛和面部鬼脸）所需的。我们的研究结果表明，诱发和自发性疼痛行为都依赖于TRPM8通道和神经元，以及在急性和慢性偏头痛模型所需的。此外，TRPM8通道的抑制预防了急性但未建立的慢性偏头痛样疼痛。这些结果与其在遗传分析中与偏头痛的相关性一致，并确定TRPM8通道是偏头痛潜在机制的组成部分。
Migraine is a complex neurovascular disorder that is one of the leading causes of disability and a reduced quality of life. Even with such a high societal impact, our understanding of the cellular and molecular mechanisms that contribute to migraine headaches is limited. To address this complex disorder, several groups have performed genome-wide association studies to elucidate migraine susceptibility genes, with many identifying transient receptor potential melastatin 8 (TRPM8), a cold-sensitive cation channel expressed in peripheral afferents innervating the trigeminovascular system, and the principal mediator of cold and cold pain associated with injury and disease. Interestingly, these migraine-associated single-nucleotide polymorphisms reside in noncoding regions of TRPM8, with those correlated with reduced migraine risk exhibiting lower TRPM8 expression and decreased cold sensitivity. Nonetheless, as a role for TRPM8 in migraine has yet to be defined, we sought to address this gap in our knowledge using mouse genetics and TRPM8 antagonism to determine whether TRPM8 channels or neurons are required for migraine-like pain (mechanical allodynia and facial grimace) in inducible migraine models. Our results show that both evoked and spontaneous pain behaviors are dependent on both TRPM8 channels and neurons, as well as required in both acute and chronic migraine models. Moreover, inhibition of TRPM8 channels prevented acute but not established chronic migraine-like pain. These results are consistent with its association with migraine in genetic analyses and establish that TRPM8 channels are a component of the underlying mechanisms of migraine.
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影响因子：
5
作者：
Burch, Rebecca C.;Loder, Stephen;Smitherman, Todd A.
通讯作者：
Smitherman, Todd A.
影响因子：
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作者：
Anttila, Verneri;Wessman, Maija;Palotie, Aarno
通讯作者：
Palotie, Aarno
影响因子：
4.9
作者：
Fuh, JL;Wang, SJ;Juang, KD
通讯作者：
Juang, KD
在妇女中与亚分类的偏头痛的遗传关联中的选择性。
影响因子：
4.5
作者：
Chasman DI;Anttila V;Buring JE;Ridker PM;Schürks M;Kurth T;International Headache Genetics Consortium
通讯作者：
International Headache Genetics Consortium
DOI：
10.1007/164_2018_201
发表时间：
2019-01-01
期刊：
CALCITONIN GENE-RELATED PEPTIDE (CGRP) MECHANISMS: FOCUS ON MIGRAINE
影响因子：
--
作者：
Edvinsson, Lars
通讯作者：
Edvinsson, Lars