F2RL1 and Headache: These immune cells release a wide range of enzymes and inflammatory factors, including mast cell tryptase, and have been proposed to be an important mediator for migraine headaches by acting on PAR2 expressed on meningeal nociceptors.22,25,63 To activate mast cells, we injected compound 48/80 into the paw 30 minutes after C781 and measured paw withdrawal thresholds and grimace scores (Fig. 5A and 5B).