Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact

Citations to this article

Meningeal lymphatic CGRP signaling governs pain via cerebrospinal fluid efflux and neuroinflammation in migraine models
Nathan P. Nelson-Maney, … , Alyssa M. Tauro, Kathleen M. Caron
Nathan P. Nelson-Maney, … , Alyssa M. Tauro, Kathleen M. Caron
Published May 14, 2024
Citation Information: J Clin Invest. 2024;134(15):e175616. https://doi.org/10.1172/JCI175616.
View: Text | PDF
Research Article Cell biology Vascular biology Article has an altmetric score of 150

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

  • Text
  • PDF
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. Interestingly, the relative abundance of mucosal vascular addressin cell adhesion molecule 1–interacting (MAdCAM1-interacting) CD4+ T cells was increased in the deep cervical lymph nodes of NTG-treated control mice but not in NTG-treated CalcrliLEC mice. Treatment of cultured hLECs with CGRP peptide in vitro induced vascular endothelial–cadherin (VE-cadherin) rearrangement and reduced functional permeability. Likewise, intra cisterna magna injection of CGRP caused rearrangement of VE-cadherin, decreased MLV uptake of cerebrospinal fluid (CSF), and impaired CSF drainage in control mice but not in CalcrliLEC mice. Collectively, these findings reveal a previously unrecognized role for lymphatics in chronic migraine, whereby CGRP signaling primes MLV-immune interactions and reduces CSF efflux.

Authors

Nathan P. Nelson-Maney, László Bálint, Anna L.S. Beeson, D. Stephen Serafin, Bryan M. Kistner, Elizabeth S. Douglas, Aisha H. Siddiqui, Alyssa M. Tauro, Kathleen M. Caron

×

Total citations by year

Year: 2025 2024 Total
Citations: 11 4 15
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2024 (4)

Title and authors Publication Year
Meningeal lymphatic vessel dysfunction driven by CGRP signaling causes migraine-like pain in mice
Jean-Leon Thomas1, 2, Emmanuelle Schindler1, and Christopher Gottschalk1
Journal of Clinical Investigation 2024
Therapeutic approaches to CNS diseases via the meningeal lymphatic and glymphatic system: prospects and challenges
Zhang R, Li J, Li X, Zhang S
Frontiers in Cell and Developmental Biology 2024
Meningeal brain borders and migraine headache genesis
Christensen SL, Levy D
Trends in neurosciences 2024
Topiramate Inhibits Capsaicin-Induced Mast Cell Degranulation and CGRP Release in Rat Dura Mater
Costa RF, Rosas EP, Paz ST, de Freitas MF, de Souza SL, de Andrade JR, de Oliveira DA, Jansen-Olesen I, Christensen SL, Valença MM
Brain Sciences 2024

Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Picked up by 16 news outlets
Blogged by 2
Posted by 41 X users
On 1 Facebook pages
16 readers on Mendeley
See more details