ArticleThe Journal of clinical investigation2024
Meningeal lymphatic CGRP signaling governs pain via cerebrospinal fluid efflux and neuroinflammation in migraine models.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
42 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- The emerging role of the meningeal lymphatic and glymphatic systems in migraine pathophysiology: a systematic review.The journal of headache and pain · 2026Pooled it
- Role of meningeal lymphatic vessels in brain homeostasis.Frontiers in immunology · 2025Pooled it
- A delayed endothelial-glial mechanism for CGRP-induced migraine.The journal of headache and pain · 2026Review
- The roles of microglia and astrocytes in inflammasomes and neurological disorders.Neural regeneration research · 2026Article
- Inflammatory Signal Persistence in Pain: Lymphatic Regulation and Neuroimmune Integration.Biology · 2026Review
- Periventricular diffusivity at the ventricular-parenchymal interface across healthy controls, episodic migraine, and chronic migraine: a cross-sectional multimodal MRI study.The journal of headache and pain · 2026Article
- New Directions in Migraine Pathophysiology: The Glymphatic System and PACAP.Life (Basel, Switzerland) · 2026Review
- Review
- Glymphatic function restored by α1-noradrenergic antagonism alleviates headache allodynia in mice.bioRxiv : the preprint server for biology · 2026Article
- The Glymphatic System and Meningeal Lymphatics: Current Understandings and Future Perspectives.MedComm · 2026Review
- Meningeal neuropeptide and neuroimmune interactions in the context of migraine.The journal of headache and pain · 2026Review
- hsa_circ_0006168 drives microglial activation in TNC via miR-99b-5p/KDM6B axis to promote central sensitization in migraine.The journal of headache and pain · 2026Article
- The neuroimmune axis and chronic pain disorders.iScience · 2026Review
- Altered perivascular-aligned diffusivity in postherpetic neuralgia assessed by the DTI-ALPS index.Frontiers in neuroscience · 2026Article
- Beyond AQP-4: convergent glymphatic-meningeal lymphatic dysfunction underlying multifactorial migraine pathogenesis.Frontiers in immunology · 2026Review
- Review
- Impaired meningeal lymphatic drainage correlates with headache intensity in episodic migraine.The journal of headache and pain · 2025Article
- Endothelial-Targeted Metallothionein-2 shRNA Nanoparticles Alleviate Migraine-Like Symptoms.CNS neuroscience & therapeutics · 2025Article
- Cerebrospinal fluid draining lymphatics in health and disease: advances and controversies.Nature cardiovascular research · 2025Review
- Brain and Immune System: Intercellular Communication During Homeostasis and Neuroimmunomodulation upon Dysfunction.International journal of molecular sciences · 2025Review
Corrections and comments
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Authors and funding
9 authors.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.