Figure 1.

MrgprB2 is expressed on meningeal mast cells and contributes to mechanical hypersensitivity in a mouse model of migraine-like pain. (A–C) Confocal images from transgenic mouse meninges in which the tdTomato (tdT) fluorescent protein is under the MrgprB2 promoter (MrgprB2 Cre tdT). (A) Avidin staining was used to identify mast cells (green). (B) MrgprB2 Cre tdT⁺ mast cells (red). The percentage of tdT⁺ cells that also were avidin-positive was 96%. Over 200 cells were counted from n = 3 mice. (C) MrgprB2 Cre tdT⁺ mast cells (red) shown near meningeal afferents (stained with Neurofilament 200, green). The scale bar is 50 μm in (A,B) and 100 μm in (C). (D,E) Representative flow cytometric profile of MrgprB2 Cre MRGPRXB2⁺ tdT⁺ (tdT⁺) mast cells. Cells were harvested from the meninges (D) or peritoneal cavity (E) and mast cells were identified as live c-kit⁺ FcεRI⁺ cells. An n = 3 of mice per group for both meningeal and peritoneal extracts. (F,G) A non-invasive dural stimulation model was used to apply Compound 48/80 (1 mg/kg) to the WT and MrgprB2^−/− (mut) mouse meninges. (F) Mechanical facial hypersensitivity was measured in male mice prior to dural injection and then 1 h, 2 h, 4 h, and 24 h after dural stimulation with Compound 48/80; WT n = 11, MrgprB2^−/− n = 10. (G) Female mice were also tested for mechanical hypersensitivity at 1 h, 2 h, 4 h, and 24 h after dural stimulation with Compound 48/80; WT n = 6, MrgprB2^−/− n = 6. Error bar: S.E.M. *p < 0.05, ****p < 0.001.