Cargando…

PACAP activates MRGPRX2 on meningeal mast cells to drive migraine-like pain

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 hav...

Descripción completa

Detalles Bibliográficos
Autores principales: Sbei, Sami, Moncrief, Taylor, Limjunyawong, Nathachit, Zeng, Yaping, Green, Dustin P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10387048/
https://www.ncbi.nlm.nih.gov/pubmed/37516794
http://dx.doi.org/10.1038/s41598-023-39571-y
_version_ 1785081801398550528
author Sbei, Sami
Moncrief, Taylor
Limjunyawong, Nathachit
Zeng, Yaping
Green, Dustin P.
author_facet Sbei, Sami
Moncrief, Taylor
Limjunyawong, Nathachit
Zeng, Yaping
Green, Dustin P.
author_sort Sbei, Sami
collection PubMed
description 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.
format Online
Article
Text
id pubmed-10387048
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-103870482023-07-31 PACAP activates MRGPRX2 on meningeal mast cells to drive migraine-like pain Sbei, Sami Moncrief, Taylor Limjunyawong, Nathachit Zeng, Yaping Green, Dustin P. Sci Rep Article 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. Nature Publishing Group UK 2023-07-29 /pmc/articles/PMC10387048/ /pubmed/37516794 http://dx.doi.org/10.1038/s41598-023-39571-y Text en © The Author(s) 2023, corrected publication 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Sbei, Sami
Moncrief, Taylor
Limjunyawong, Nathachit
Zeng, Yaping
Green, Dustin P.
PACAP activates MRGPRX2 on meningeal mast cells to drive migraine-like pain
title PACAP activates MRGPRX2 on meningeal mast cells to drive migraine-like pain
title_full PACAP activates MRGPRX2 on meningeal mast cells to drive migraine-like pain
title_fullStr PACAP activates MRGPRX2 on meningeal mast cells to drive migraine-like pain
title_full_unstemmed PACAP activates MRGPRX2 on meningeal mast cells to drive migraine-like pain
title_short PACAP activates MRGPRX2 on meningeal mast cells to drive migraine-like pain
title_sort pacap activates mrgprx2 on meningeal mast cells to drive migraine-like pain
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10387048/
https://www.ncbi.nlm.nih.gov/pubmed/37516794
http://dx.doi.org/10.1038/s41598-023-39571-y
work_keys_str_mv AT sbeisami pacapactivatesmrgprx2onmeningealmastcellstodrivemigrainelikepain
AT moncrieftaylor pacapactivatesmrgprx2onmeningealmastcellstodrivemigrainelikepain
AT limjunyawongnathachit pacapactivatesmrgprx2onmeningealmastcellstodrivemigrainelikepain
AT zengyaping pacapactivatesmrgprx2onmeningealmastcellstodrivemigrainelikepain
AT greendustinp pacapactivatesmrgprx2onmeningealmastcellstodrivemigrainelikepain