PDF(Pubmed)
Abstract：
Although the introduction of drugs targeting calcitonin gene-related peptide (CGRP) revolutionized migraine treatment, still a substantial proportion of migraine patients do not respond satisfactorily to such a treatment, and new therapeutic targets are needed. Therefore, molecular studies on migraine pathogenesis are justified. Oxidative stress is implicated in migraine pathogenesis, as many migraine triggers are related to the production of reactive oxygen and nitrogen species (RONS). Migraine has been proposed as a superior mechanism of the brain to face oxidative stress resulting from energetic imbalance. However, the precise mechanism behind the link between migraine and oxidative stress is not known. Nociceptive primary afferent nerve fiber endings express ion channel receptors that change harmful stimuli into electric pain signals. Transient receptor potential cation channel subfamily A member 1 (TRPA1) is an ion channel that can be activated by oxidative stress products and stimulate the release of CGRP from nerve endings. It is a transmembrane protein with ankyrin repeats and conserved cysteines in its N-terminus embedded in the cytosol. TRPA1 may be a central element of the signaling pathway from oxidative stress and NO production to CGRP release, which may play a critical role in headache induction. In this narrative review, we present information on the role of oxidative stress in migraine pathogenesis and provide arguments that TRPA1 may be \"a missing link\" between oxidative stress and migraine and therefore a druggable target in this disease.
摘要：
尽管针对降钙素基因相关肽（CGRP）的药物的引入彻底改变了偏头痛的治疗方法，仍然有相当比例的偏头痛患者对这种治疗没有令人满意的反应，需要新的治疗靶点。因此,关于偏头痛发病机制的分子研究是有道理的。氧化应激与偏头痛的发病机制有关，许多偏头痛的触发因素与活性氧和氮（RONS）的产生有关。偏头痛已被认为是大脑面对由能量失衡引起的氧化应激的优良机制。然而,偏头痛与氧化应激之间联系的确切机制尚不清楚。伤害性初级传入神经纤维末梢表达离子通道受体，将有害刺激改变为电疼痛信号。瞬时受体电位阳离子通道亚家族A成员1（TRPA1）是一种离子通道，可被氧化应激产品激活并刺激CGRP从神经末梢释放。它是一种跨膜蛋白，具有锚蛋白重复序列，其N末端保守的半胱氨酸嵌入胞质溶胶中。TRPA1可能是氧化应激和NO产生到CGRP释放的信号通路的核心元件，这可能在头痛诱发中起关键作用。在这篇叙述性评论中，我们提供了有关氧化应激在偏头痛发病机制中的作用的信息,并提供了TRPA1可能是氧化应激和偏头痛之间的"缺失环节"的论点,因此是该疾病的可药物靶标.
