PACAP activates MRGPRX2 on meningeal mast cells to drive migraine-like pain
Issued Date
2023-12-01
Resource Type
eISSN
20452322
Scopus ID
2-s2.0-85165982099
Pubmed ID
37516794
Journal Title
Scientific Reports
Volume
13
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Scientific Reports Vol.13 No.1 (2023)
Suggested Citation
Sbei S., Moncrief T., Limjunyawong N., Zeng Y., Green D.P. PACAP activates MRGPRX2 on meningeal mast cells to drive migraine-like pain. Scientific Reports Vol.13 No.1 (2023). doi:10.1038/s41598-023-39571-y Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/88244
Title
PACAP activates MRGPRX2 on meningeal mast cells to drive migraine-like pain
Author(s)
Author's Affiliation
Other Contributor(s)
Abstract
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.