Targeting PACAP: Beyond Migraine to Cluster, Menstrual, and Post-traumatic Headaches

IF 3.4 3区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in Therapy Pub Date : 2025-03-18 DOI:10.1007/s12325-025-03166-y

Lanfranco Pellesi, Mona Ameri Chalmer, Song Guo, Thien Phu Do, Zheman Xiao, Paolo Martelletti

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引用次数: 0

Abstract

The pituitary adenylate cyclase-activating peptide (PACAP) pathway is a critical focus in the pathophysiology of several headache disorders. PACAP influences headache pathophysiology through interactions with distinct receptors (PAC₁, VPAC₁, and VPAC₂) and pathways linked to neurovascular and hormonal regulation. Evidence supports its role in the modulation of trigeminal and parasympathetic systems, implicated in cluster headaches and menstrual migraine, and its involvement in sensitizing pain pathways post trauma in post-traumatic headaches. Early clinical trials targeting PACAP signaling show promise, with one study demonstrating efficacy in migraine prophylaxis. This narrative review synthesizes current evidence while addressing gaps in understanding PACAP’s precise mechanisms. Future research should prioritize expanding the scope of PACAP-focused investigations across diverse headache types, aiming to establish it as a therapeutic target for several headache disorders. Success in ongoing and future trials could redefine headache management for millions of underserved patients worldwide.

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靶向PACAP：从偏头痛到丛集性、经期和创伤后头痛。

垂体腺苷酸环化酶激活肽（PACAP）途径是几种头痛疾病病理生理学的关键焦点。PACAP通过与不同的受体（PAC1、VPAC1和VPAC2）以及与神经血管和激素调节相关的途径相互作用影响头痛病理生理。证据支持其在三叉神经和副交感神经系统的调节中所起的作用，涉及丛集性头痛和经期偏头痛，并参与创伤后头痛的创伤后疼痛通路的敏感化。针对PACAP信号的早期临床试验显示出希望，其中一项研究表明在偏头痛预防方面有效。这篇叙述性综述综合了目前的证据，同时解决了理解PACAP精确机制的差距。未来的研究应优先扩大以pacap为重点的不同头痛类型的研究范围，旨在将其作为几种头痛疾病的治疗靶点。正在进行和未来试验的成功可能会重新定义全球数百万治疗不足患者的头痛管理。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Advances in Therapy 医学-药学

CiteScore

7.20

自引率

2.60%

发文量

353

审稿时长

6-12 weeks

期刊介绍： Advances in Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of therapeutics and interventions (including devices) across all therapeutic areas. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Advances in Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research.