Protease activated receptor 2 (PAR2) activation causes migraine-like pain behaviors in mice

Cephalalgia : an International Journal of Headache
Shayne N HasslerGregory Dussor

Abstract

Pain is the most debilitating symptom of migraine. The cause of migraine pain likely requires activation of meningeal nociceptors. Mast cell degranulation, with subsequent meningeal nociceptor activation, has been implicated in migraine pathophysiology. Degranulating mast cells release serine proteases that can cleave and activate protease activated receptors. The purpose of these studies was to investigate whether protease activated receptor 2 is a potential generator of nociceptive input from the meninges by using selective pharmacological agents and knockout mice. Ratiometric Ca++ imaging was performed on primary trigeminal and dural cell cultures after application of 2at-LIGRL-NH2, a specific protease activated receptor 2 agonist. Cutaneous hypersensitivity and facial grimace was measured in wild-type and protease activated receptor 2-/- mice after dural application of 2at-LIGRL-NH2 or compound 48-80, a mast cell degranulator. Behavioral experiments were also conducted in mice after dural application of 2at-LIGRL-NH2 (2AT) in the presence of either C391, a selective protease activated receptor 2 antagonist, or sumatriptan. 2at-LIGRL-NH2 evoked Ca2+ signaling in mouse trigeminal neurons, dural fibroblasts and in meningeal af...Continue Reading

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Citations

Sep 2, 2020·Neuroscience Bulletin·Mamoru Shibata, Chunhua Tang
Apr 12, 2019·Pharmaceuticals·Silvia Benemei, Greg Dussor
Aug 30, 2019·The Journal of Headache and Pain·Andrea M HarriottPhilip R Holland
Jan 12, 2021·The Journal of Pain : Official Journal of the American Pain Society·Juliet MwirigiTheodore J Price
Apr 4, 2021·Animals : an Open Access Journal From MDPI·Alexandra L WhittakerTimothy H Barker
Jun 27, 2021·Brain, Behavior, and Immunity·Thomas A Szabo-PardiMichael D Burton
Jun 29, 2021·Frontiers in Cellular Neuroscience·Lijia MaiWenguo Fan
Aug 29, 2021·Pharmaceuticals·Diéssica Padilha DalenogareGabriela Trevisan
Nov 26, 2021·Cephalalgia : an International Journal of Headache·Lanfranco PellesiMessoud Ashina

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Methods Mentioned

BETA
transgenic

Software Mentioned

Olympus
Graph Pad Prism
GPower

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