MRGPRX2 Mediates Mast Cell‐Induced Endometriosis Pain Through the Sensitization of Sensory Neurons via Histamine/ HRH1 / TRPV1 Signaling Pathway

Xinqi Mao, Jianzhang Wang, Shaojie Ding, Xinyue Guo, Xinxin Xu, Ping Xu, Xinmei Zhang
FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025 · vol. 39(13) , pp. e70778 · doi:10.1096/fj.202501493r · PMID:40600649 · W4411929792
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⚙ AI-generated summary by claude@2026-06, 2026-06-08 ⓘ

MRGPRX2 on mast cells mediates endometriosis pain by sensitizing sensory neurons via histamine, HRH1, and TRPV1 signaling, indicating it as a potential therapeutic target.

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Abstract

The studies on how mast cells mediate endometriosis pain are still limited. Mas-related G protein-coupled receptor member X2 (MRGPRX2), a receptor expressed on mast cells, participates in pain, inflammation, and itch. However, it is still unclear whether and how MRGPRX2 mediates endometriosis pain. Here, we found that the knockout of mast cells alleviated endometriosis-induced hyperalgesia. The density of MRGPRX2-positive mast cells was increased in endometriotic lesions. HBD-2 was secreted from endometriotic cells. Upon HBD-2 treatment, a significant increase in histamine release in the culture supernatant of HMC1.1 cells was detected, whereas no change in histamine levels was observed in the supernatant of MRGPRX2 KO cells. An incubation with histamine increased Ca2+ influx in DRG cells in vitro, whereas desloratadine reversed this process. In Mrgprb2-deficient endometriosis model mice, gene ablation effectively alleviated hyperalgesia and reduced the size of endometriotic lesions. Overall, MRGPRX2 mediates cell-induced endometriosis pain through sensory neurons sensitization via the histamine/HRH1/TRPV1 signaling pathway and can serve as a novel therapeutic target for endometriosis pain.

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Outcome instruments

VAS-pain

Condition tags

mesh:D004715endometriosis

MeSH descriptors

Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

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