Benemei S, Fusi C, Trevisan Gabriela, Geppetti Pierangelo
Clinical Pharmacology Unit, Department of Health Sciences, University of Florence, Florence, Italy; Headache Centre, Department of Health Sciences, University of Florence, Florence, Italy.
Br J Pharmacol. 2014 May;171(10):2552-67. doi: 10.1111/bph.12512.
Migraine remains an elusive and poorly understood disease. The uncertainty is reflected by the currently unsatisfactory acute and prophylactic treatments for this disease. Genetic and pharmacological information points to the involvement of some transient receptor potential (TRP) channels in pain mechanisms. In particular, the TRP vanilloid 1 (TRPV1) and TRP ankyrin 1 (TRPA1) channels seem to play a major role in different models of pain diseases. Recent findings have underscored the possibility that TRP channels expressed in the nerve terminals of peptidergic nociceptors contribute to the migraine mechanism. Among this channel subset, TRPA1, a sensor of oxidative, nitrative and electrophilic stress, is activated by an unprecedented series of irritant and pain-provoking exogenous and endogenous agents, which release the pro-migraine peptide, calcitonin gene-related peptide, through this neuronal pathway. Some of the recently identified TRPA1 activators have long been known as migraine triggers. Furthermore, specific analgesic and antimigraine medicines have been shown to inhibit or desensitize TRPA1 channels. Thus, TRPA1 is emerging as a major contributing pathway in migraine and as a novel target for the development of drugs for pain and migraine treatment.
偏头痛仍然是一种难以捉摸且了解甚少的疾病。这种不确定性体现在目前针对该疾病的急性和预防性治疗并不令人满意。遗传学和药理学信息表明，一些瞬时受体电位（TRP）通道参与了疼痛机制。特别是，TRP香草酸受体1（TRPV1）和TRP锚蛋白1（TRPA1）通道似乎在不同的疼痛疾病模型中起主要作用。最近的研究结果强调了肽能伤害感受器神经末梢中表达的TRP通道促成偏头痛机制的可能性。在这个通道亚群中，TRPA1作为氧化、硝化和亲电应激的感受器，被一系列前所未有的刺激性和致痛性外源性和内源性物质激活，这些物质通过这条神经元途径释放促偏头痛肽——降钙素基因相关肽。一些最近确定的TRPA1激活剂长期以来一直被认为是偏头痛的触发因素。此外，特定的镇痛和抗偏头痛药物已被证明可以抑制TRPA1通道或使其脱敏。因此，TRPA1正在成为偏头痛的一个主要促成途径，并成为开发用于疼痛和偏头痛治疗药物的新靶点。
