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TRP Channels and Migraine: Recent Developments and New Therapeutic Opportunities

机译:TRP渠道和偏头痛:最新发展和新的治疗机会

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Migraine is the second-most disabling disease worldwide, and the second most common neurological disorder. Attacks can last many hours or days, and consist of multiple symptoms including headache, nausea, vomiting, hypersensitivity to stimuli such as light and sound, and in some cases, an aura is present. Mechanisms contributing to migraine are still poorly understood. However, transient receptor potential (TRP) channels have been repeatedly linked to the disorder, including TRPV1, TRPV4, TRPM8, and TRPA1, based on their activation by pathological stimuli related to attacks, or their modulation by drugsatural products known to be efficacious for migraine. This review will provide a brief overview of migraine, including current therapeutics and the link to calcitonin gene-related peptide (CGRP), a neuropeptide strongly implicated in migraine pathophysiology. Discussion will then focus on recent developments in preclinical and clinical studies that implicate TRP channels in migraine pathophysiology or in the efficacy of therapeutics. Given the use of onabotulinum toxin A (BoNTA) to treat chronic migraine, and its poorly understood mechanism, this review will also cover possible contributions of TRP channels to BoNTA efficacy. Discussion will conclude with remaining questions that require future work to more fully evaluate TRP channels as novel therapeutic targets for migraine.
机译:偏头痛是全球第二大致残性疾病,也是第二大最常见的神经系统疾病。发作可能持续数小时或数天,并且由多种症状组成,包括头痛,恶心,呕吐,对光和声音等刺激过敏,在某些情况下会出现先兆。导致偏头痛的机制仍知之甚少。但是,暂时性受体电位(TRP)通道已被反复关联到该疾病,包括TRPV1,TRPV4,TRPM8和TRPA1,这是由于它们被与发作有关的病理刺激所激活,或者被已知有效的药物/天然产物所调节偏头痛本文将对偏头痛进行简要概述,包括当前的治疗方法以及与降钙素基因相关肽(CGRP)的链接,降钙素基因相关肽是与偏头痛的病理生理密切相关的神经肽。然后,讨论将集中于临床前和临床研究的最新进展,这些进展暗示着偏头痛病理生理学或治疗功效中的TRP通道。鉴于使用肉毒杆菌毒素A(BoNTA)来治疗慢性偏头痛,其机理尚不清楚,因此该综述还将涵盖TRP通道对BoNTA功效的可能贡献。讨论将以尚待解决的剩余问题结束,这些问题需要未来的工作来更全面地评估TRP通道作为偏头痛的新型治疗靶标。

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