Thomas Jean-Leon, Schindler Emmanuelle Ad, Gottschalk Christopher
Department of Neurology, Yale University School of Medicine, New Haven, Connecticut, USA.
Paris Brain Institute, Université Pierre et Marie Curie Paris 06 UMRS1127, Sorbonne Université, Paris, France.
J Clin Invest. 2024 Aug 1;134(15):e182556. doi: 10.1172/JCI182556.
Migraines are a type of headache that occur with other neurological symptoms, but the pathophysiology remains unclear. In this issue of the JCI, Nelson-Maney and authors used constitutive and inducible knockouts of the CGRP receptor components, elegantly demonstrating an essential function of CGRP in modulating meningeal lymphatic vessels (MLVs) in migraine. CGRP was shown to induce rearrangement of membrane-bound gap junction proteins in MLVs, resulting in a reduced CSF flux into cervical lymph nodes. The authors also provided evidence of a primary role for CGRP in modulating neuro-immune function. Finally, by showing that blocking CGRP signaling in MLVs attenuated pain behavior associated with acute migraine in rodents, the authors provided a target for pharmacological blockade of CGRP in relation to primary headache disorders.
偏头痛是一种伴有其他神经症状的头痛类型，但其病理生理学仍不清楚。在本期《临床研究杂志》中，纳尔逊 - 梅尼及其作者使用了降钙素基因相关肽（CGRP）受体成分的组成型和诱导型基因敲除技术，巧妙地证明了CGRP在偏头痛中调节脑膜淋巴管（MLV）的重要功能。研究表明，CGRP可诱导MLV中膜结合间隙连接蛋白的重排，导致脑脊液流入颈淋巴结的通量减少。作者还提供了证据，证明CGRP在调节神经免疫功能中起主要作用。最后，通过表明阻断MLV中的CGRP信号可减轻与啮齿动物急性偏头痛相关的疼痛行为，作者提供了针对原发性头痛疾病进行CGRP药理学阻断的靶点。
