ASICs as therapeutic targets for migraine.

ASICs as therapeutic targets for migraine.
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DOI:
10.1016/j.neuropharm.2014.12.015
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发表时间:
2015-07
期刊:
影响因子:
4.7
通讯作者:
Dussor G
Dussor G
中科院分区:
医学2区
文献类型:
--
作者:
Dussor G

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偏头痛是最常见的神经系统疾病,也是最常见的慢性疼痛症状之一。尽管偏头痛很普遍,但人们对导致偏头痛的病理生理学知之甚少,而且新的治疗靶点的确定也很缓慢。目前认为有几个过程与偏头痛有关,包括下丘脑活动改变,皮质扩散抑制(CSD),以及来自颅脑的传入感觉输入。细胞外pH的降低和随后的酸敏感离子通道(ASIC)的激活可能参与了这些过程中的每一个过程,因此可能在偏头痛的病理生理学中发挥作用。虽然很少有研究直接研究ASIC在偏头痛中的作用,但直接研究ASIC在偏头痛中的作用的研究已经产生了令人振奋的结果,包括ASIC阻滞剂在临床前偏头痛模型和人类偏头痛患者中的有效性。这篇综述的目的是讨论偏头痛的病理生理学机制,以及与这些事件有关的pH降低和/或ASICs的发现,并提出在未来ASICs和偏头痛的研究中需要解决的问题。
Migraine is the most common neurological disorder and one of the most common chronic pain conditions. Despite its prevalence, the pathophysiology leading to migraine is poorly understood and the identification of new therapeutic targets has been slow. Several processes are currently thought to contribute to migraine including altered activity in the hypothalamus, cortical-spreading depression (CSD), and afferent sensory input from the cranial meninges. Decreased extracellular pH and subsequent activation of acid-sensing ion channels (ASICs) may contribute to each of these processes and may thus play a role in migraine pathophysiology. Although few studies have directly examined a role of ASICs in migraine, studies directly examining a connection have generated promising results including efficacy of ASIC blockers in both preclinical migraine models and in human migraine patients. The purpose of this review is to discuss the pathophysiology thought to contribute to migraine and findings that implicate decreased pH and/or ASICs in these events, as well as propose issues to be resolved in future studies of ASICs and migraine.
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