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PACAP activates MRGPRX2 on meningeal mast cells to drive migraine-like pain
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PACAP activates MRGPRX2 on meningeal mast cells to drive migraine-like pain
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Journal Article
PACAP activates MRGPRX2 on meningeal mast cells to drive migraine-like pain
2023
Overview
Migraine ranks among the most prevalent disorders worldwide, leading to disability and decreased quality of life in patients. Recently, neurogenic inflammation has been recognized as a potential underlying pathology contributing to the migraine pain pathway. Mast cells reside in the meninges and have been implicated in contributing to the pathophysiology of migraine. Here we report for the first time that the mouse Mas-Related G-protein-coupled Receptor B2 (MrgprB2), is expressed on meningeal connective tissue mast cells and contributes to Pituitary Adenylate Cyclase Activating Peptide (PACAP)-induced migraine-like pain behavior. We also found that PACAP was able to dose-dependently lead to enzyme release from human mast cells via activation of MRGPRX2; the human homolog of MrgprB2. Using a transgenic MRGPRX2 mouse, we observed significant increases in PACAP-induced migraine-like pain behavior in MRGPRX2
+
mice vs mice lacking the receptor. These results reveal both MrgprB2 and MRGPRX2 as important contributors to neuropeptide-induced migraine pain.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ Animals
/ Cells
/ Headache
/ Humanities and Social Sciences
/ Humans
/ Meninges
/ Mice
/ Migraine
/ Migraine Disorders - chemically induced
/ Nerve Tissue Proteins - genetics
/ Pain
/ Peptides
/ Pituitary adenylate cyclase-activating polypeptide
/ Pituitary Adenylate Cyclase-Activating Polypeptide - genetics
/ Receptors, G-Protein-Coupled - genetics
/ Receptors, Neuropeptide - genetics
/ Science
