Evidence map›Paper›PMID 40419944›Full record

ArticleThe journal of headache and pain2025

Fibroblast reprogramming in the dura mater of NTG-induced migraine-related chronic hypersensitivity model drives monocyte infiltration via Angptl1-dependent stromal signaling.

Guangyu Guo, Lei Zhang, Xuyang Liu, Yiping Deng, Peiyu Wu, Ruofan Zhao, Wei Wang

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PubMed Full text at PMC Publisher
In one paragraph

Article in The journal of headache and pain, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Selective loss and transcriptional reprogramming of Nox4The journal of headache and pain · 2025
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Guangyu Guo *Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.ORCID http://orcid.org/0000-0003-3079-8474
Lei Zhang *Clinical Systems Biology Laboratories, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Xuyang LiuDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Yiping DengClinical Systems Biology Laboratories, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Peiyu WuClinical Systems Biology Laboratories, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Ruofan ZhaoAcademy of Medical Sciences of Zhengzhou University, Zhengzhou, China.
Wei WangHeadache Center, Department of Neurology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China. weiwang336776@zju.edu.cn.ORCID http://orcid.org/0000-0003-2302-6273

Funding

Joint Construction Project of Medical Science and Technology Research of Henan Province LHGJ20210289Zhejiang University School of Medicine Affiliated Sir Run Run Shaw Hospital Cultivation Project YQNPY24238
6 · The paper itself

Abstract

backgroundMigraine, characterized by recurrent episodes of severe headache, remains mechanistically enigmatic. While traditional theories emphasize trigeminovascular activation, the role of meningeal stromal-immune crosstalk in disease chronicity is poorly understood.

methodsA migraine-related chronic hypersensitivity model was utilized via intermittent intraperitoneal nitroglycerin (NTG, 10 mg/kg, every other day for 9 days) and peripheral mechanical hypersensitivity was assessed using von Frey filaments. Single-cell RNA sequencing (scRNA-seq) was performed on dura tissues to construct a cellular atlas of NTG-induced remodeling. These data were then integrated with migraine genome-wide association study (GWAS) risk genes, cell-cell interaction networks, and transcriptional regulation analysis to dissect NTG-driven meningeal remodeling.

resultsThe NTG-induced migraine-related chronic hypersensitivity model demonstrated sustained mechanical allodynia, as evidenced by significantly decreased paw withdrawal thresholds (p < 0.0001). Single-cell profiling of the dura mater revealed a 2.4-fold expansion of a pro-inflammatory fibroblast subpopulation (Fibro_c5: 1.9% in Vehicle vs. 4.6% in NTG group), which exhibited marked activation of TNF-α/NF-κB signaling pathways (normalized enrichment score [NES] = 1.83). Concomitantly, we observed an 82% increase in meningeal monocytes (5.7-10.4%) that showed preferential interaction with Fibro_c5 fibroblasts through Angptl1-mediated stromal-immune crosstalk (log2 fold change = 1.41). Regulatory network analysis identified Mafk as the upstream transcriptional regulator orchestrating Angptl1 expression in this pathological communication axis.

conclusionOur study reveals that NTG reprograms meningeal fibroblasts to expand a pro-inflammatory fibroblast subtype, which drives migraine-related chronic hypersensitivity through TNF-α/NF-κB signaling and Angptl1-mediated monocyte crosstalk. The identified Mafk-Angptl1 axis presents a potential therapeutic target, though human validation remains essential.

Indexed as

Angiopoietin-like ProteinsCellular ReprogrammingDura MaterFibroblastsHyperalgesiaMigraine DisordersMonocytesAnimalsDisease Models, AnimalMaleMiceNitroglycerinSignal TransductionAngiopoietin-like ProteinsNitroglycerinDuraFibroblast reprogrammingMigraine-related chronic hypersensitivityscRNA-seq

Identifiers

PMID40419944
PMCPMC12105374

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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.