Migraine is a disabling neurological disorder that affects more than one billion people worldwide. The clinical presentation is characterized by recurrent headache attacks, which are often accompanied by photophobia, phonophobia, nausea and vomiting. Although the pathogenesis of migraine remains incompletely understood, mounting evidence suggests that specific signalling molecules are involved in the initiation and modulation of migraine attacks. These signalling molecules include pituitary adenylate cyclase-activating polypeptide (PACAP), a vasoactive peptide that is known to induce migraine attacks when administered by intravenous infusion to people with migraine. Discoveries linking PACAP to migraine pathogenesis have led to the development of drugs that target PACAP signalling, and a phase II trial has provided evidence that a monoclonal antibody against PACAP is effective for migraine prevention. In this Review, we explore the molecular and cellular mechanisms of PACAP signalling, shedding light on its role in the trigeminovascular system and migraine pathogenesis. We then discuss emerging therapeutic strategies that target PACAP signalling for the treatment of migraine and consider the research needed to translate the current knowledge into a treatment for migraine in the clinic.

偏头痛是一种致残性神经系统疾病，影响着全球超过 10 亿人。临床表现以反复发作的头痛为特征，常伴有畏光、畏声、恶心和呕吐。尽管偏头痛的发病机制仍不完全清楚，但越来越多的证据表明，特定的信号分子参与偏头痛发作的启动和调节。这些信号分子包括垂体腺苷酸环化酶激活多肽 （PACAP），这是一种血管活性肽，已知在通过静脉输注给偏头痛患者时会诱发偏头痛发作。将 PACAP 与偏头痛发病机制联系起来的发现导致了靶向 PACAP 信号传导的药物的开发，一项 II 期试验提供了证据表明，针对 PACAP 的单克隆抗体对偏头痛预防有效。在这篇综述中，我们探讨了 PACAP 信号传导的分子和细胞机制，阐明了它在三叉神经血管系统和偏头痛发病机制中的作用。然后，我们讨论了针对 PACAP 信号治疗偏头痛的新兴治疗策略，并考虑了将当前知识转化为临床偏头痛治疗所需的研究。