Edvinsson Lars
Division of Experimental Vascular Research, Department of Clinical Sciences, Lund University, Lund, Sweden.
Department of Clinical Experimental Research, Glostrup Research Institute, Glostrup Hospital, Glostrup, Denmark.
Handb Exp Pharmacol. 2019;255:121-130. doi: 10.1007/164_2018_201.
Migraine is a common neurological disorder that afflicts up to 15% of the adult population in most countries, with predominance in females. It is characterized by episodic, often disabling headache, photophobia and phonophobia, autonomic symptoms (nausea and vomiting), and in a subgroup an aura in the beginning of the attack. Although still debated, many researchers consider migraine to be a disorder in which CNS dysfunction plays a pivotal role while various parts of the trigeminal system are necessary for the expression of associated symptoms.Treatment of migraine has in recent years seen the development of drugs that target the trigeminal sensory neuropeptide calcitonin gene-related peptide (CGRP) or its receptor. Several of these drugs are now approved for use in frequent episodic and in chronic migraine. CGRP-related therapies offer considerable improvements over existing drugs, as they are the first to be designed specifically to act on the trigeminal pain system: they are more specific and have little or no adverse effects. Small molecule CGRP receptor antagonists, gepants, are effective for acute relief of migraine headache, whereas monoclonal antibodies against CGRP (Eptinezumab, Fremanezumab, and Galcanezumab) or the CGRP receptor (Erenumab) effectively prevent migraine attacks. The neurobiology of CGRP signaling is briefly summarized together with key clinical evidence for the role of CGRP in migraine headache, including the efficacy of CGRP-targeted treatments.
偏头痛是一种常见的神经系统疾病,在大多数国家,多达15%的成年人受其困扰,女性更为多见。其特征为发作性、常使人丧失能力的头痛、畏光和畏声、自主神经症状(恶心和呕吐),在一部分患者中,发作开始时会出现先兆。尽管仍存在争议,但许多研究人员认为偏头痛是一种中枢神经系统功能障碍起关键作用的疾病,而三叉神经系统的各个部分对于相关症状的表现是必需的。近年来,偏头痛的治疗出现了针对三叉神经感觉神经肽降钙素基因相关肽(CGRP)或其受体的药物。其中几种药物现已被批准用于频繁发作性和慢性偏头痛。与CGRP相关的疗法比现有药物有显著改善,因为它们是首批专门设计用于作用于三叉神经疼痛系统的药物:它们更具特异性,几乎没有或没有副作用。小分子CGRP受体拮抗剂(gepants)对偏头痛头痛的急性缓解有效,而抗CGRP单克隆抗体(依普奈珠单抗、夫雷奈珠单抗和加卡奈珠单抗)或抗CGRP受体单克隆抗体(erenumab)能有效预防偏头痛发作。本文简要总结了CGRP信号传导的神经生物学以及CGRP在偏头痛头痛中作用的关键临床证据,包括针对CGRP治疗的疗效。