Danish Headache Center, Department of Neurology, Translational Research Center, Rigshospitalet-Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Glostrup, Denmark.
Department of Neurology, Zealand University Hospital, Roskilde, Denmark.
Eur J Neurol. 2024 Aug;31(8):e16333. doi: 10.1111/ene.16333. Epub 2024 Jun 18.
This review will explore the categorization of migraine-provoking molecules, their cellular actions, site of action and potential drug targets based on the migraine cascade model.
Personal experience and literature.
Migraine impacts over 1 billion people worldwide but is underfunded in research. Recent progress, particularly through the human and animal provocation model, has deepened our understanding of its mechanisms. This model have identified endogenous neuropeptides such as calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating peptide (PACAP) that induces controlled migraine-like attacks leading to significant discoveries of their role in migraine. This knowledge led to the development of CGRP-inhibiting drugs; a groundbreaking migraine treatment now accessible globally. Also a PACAP-inhibiting drug was effective in a recent phase II trial. Notably, rodent studies have shed light on pain pathways and the mechanisms of various migraine-inducing substances identifying novel drug targets. This is primarily done by using selective inhibitors that target specific signaling pathways of the known migraine triggers leading to the hypothesized cellular cascade model of migraine.
The model of migraine presents numerous opportunities for innovative drug development. The future of new migraine treatments is limited only by the investment from pharmaceutical companies.
本综述将根据偏头痛级联模型，探讨偏头痛诱发分子的分类、细胞作用、作用部位和潜在的药物靶点。
个人经验和文献。
偏头痛影响着全球超过 10 亿人，但在研究方面资金投入不足。最近的进展，特别是通过人类和动物诱发模型，加深了我们对其机制的理解。该模型已确定了内源性神经肽，如降钙素基因相关肽（CGRP）和垂体腺苷酸环化酶激活肽（PACAP），它们引发可控的偏头痛样发作，从而对其在偏头痛中的作用有了重大发现。这一知识促成了 CGRP 抑制剂药物的开发；一种突破性的偏头痛治疗方法现在在全球范围内都可以获得。此外，一种 PACAP 抑制剂药物在最近的 II 期临床试验中也有效。值得注意的是，啮齿动物研究揭示了疼痛途径和各种诱发偏头痛物质的机制，确定了新的药物靶点。这主要是通过使用选择性抑制剂来靶向已知偏头痛触发物的特定信号通路，从而导致假设的偏头痛细胞级联模型。
偏头痛模型为创新药物开发提供了众多机会。新的偏头痛治疗方法的未来仅受制药公司投资的限制。
