Meningeal lymphatic CGRP signaling governs pain via cerebrospinal fluid efflux and neuroinflammation in migraine models.

ABSTRACT: Recently developed antimigraine therapeutics targeting calcitonin gene-related peptide (CGRP) signaling are effective, though their sites of activity remain elusive. Notably, the lymphatic vasculature is responsive to CGRP signaling, but whether meningeal lymphatic vessels (MLVs) contribute to migraine pathophysiology is unknown. Mice with lymphatic vasculature deficient in the CGRP receptor (CalcrliLEC mice) treated with nitroglycerin-mediated (NTG-mediated) chronic migraine exhibit reduced pain and light avoidance compared with NTG-treated littermate controls. Gene expression profiles of lymphatic endothelial cells (LECs) isolated from the meninges of Rpl22HA/+;Lyve1Cre RiboTag mice treated with NTG revealed increased MLV-immune interactions compared with cells from untreated mice. Inter

SUBMITTER: Nelson-Maney NP 

PROVIDER: S-EPMC11290972 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature