Targeting TRP channels for novel migraine therapeutics.
Targeting TRP channels for novel migraine therapeutics.
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DOI：
10.1021/cn500083e
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发表时间：
2014-11-19
影响因子：
5
通讯作者：
Porreca, Frank
中科院分区：
文献类型：
--
作者：
Dussor, Gregory;Yan, J.;Xie, Jennifer Y.;Ossipov, Michael H.;Dodick, David W.;Porreca, Frank
偏头痛越来越多地被认为是一种大脑疾病。在易感个体中，多种“触发物”可影响改变的中枢兴奋性，导致血管周围三叉神经伤害性传入的激活和敏化（即，三叉神经血管系统），导致偏头痛。瞬时受体电位（TRP）通道在硬膜传入的一个子集中表达，包括含有降钙素基因相关肽（CGRP）的那些。TRP通道的激活促进伤害性传入纤维的兴奋并潜在地导致疼痛。除了疼痛之外，对机械和冷刺激的异常性疼痛可以由外周传入和中枢疼痛通路的敏化引起。TRP通道响应于多种内源性条件，包括化学介质和低pH值。这些通道可以被外源性刺激激活，包括广泛的化学和环境刺激物，其中一些已被证明可引发人类偏头痛。TRP通道的激活可以引起CGRP释放，并且已经证明通过受体拮抗剂或抗体策略阻断CGRP的作用在治疗偏头痛中是有效的。识别可以阻止TRP通道激活的方法为发现偏头痛治疗方法提供了额外的新策略。
Migraine is increasingly understood to be a disorder of the brain. In susceptible individuals, a variety of “triggers” may influence altered central excitability, resulting in the activation and sensitization of trigeminal nociceptive afferents surrounding blood vessels (i.e., the trigeminovascular system), leading to migraine pain. Transient receptor potential (TRP) channels are expressed in a subset of dural afferents, including those containing calcitonin gene related peptide (CGRP). Activation of TRP channels promotes excitation of nociceptive afferent fibers and potentially lead to pain. In addition to pain, allodynia to mechanical and cold stimuli can result from sensitization of both peripheral afferents and of central pain pathways. TRP channels respond to a variety of endogenous conditions including chemical mediators and low pH. These channels can be activated by exogenous stimuli including a wide range of chemical and environmental irritants, some of which have been demonstrated to trigger migraine in humans. Activation of TRP channels can elicit CGRP release, and blocking the effects of CGRP through receptor antagonism or antibody strategies has been demonstrated to be effective in the treatment of migraine. Identification of approaches that can prevent activation of TRP channels provides an additional novel strategy for discovery of migraine therapeutics.
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DOI：
10.3988/jcn.2012.8.2.89
发表时间：
2012-06
期刊：
Journal of clinical neurology (Seoul, Korea)
影响因子：
--
作者：
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通讯作者：
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影响因子：
5.3
作者：
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DOI：
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发表时间：
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期刊：
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影响因子：
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影响因子：
18.2
作者：
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影响因子：
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