What do we already know about this topic?

• Migraine pain is thought to ultimately require activation of nociceptors in the cranial meninges.
• This process likely involves dural mast cell (MC) degranulation and secretion of inflammatory mediators, cytokines, chemokines and proteases that activate nociceptors.
• Tryptase, the most abundant MC protease, has been shown to stimulate additional MC as well as trigeminal nociceptors by activating the protease-activated receptors 2 (PAR-2) receptor.^1,2
• Mast cell or neuronal PAR-2 receptors may, therefore, represent a novel target for migraine treatment.

How was this study conducted?

• In-vivo study conducted in 6-week-old female C57BL/6 mice injected with a fully humanized PAR-2 monoclonal antibody (mAb) either 72 hours before the first restraint-stress, or 72 hours before umbellulone inhalational exposure, to determine the contribution of PAR-2 receptors in preventing (a) restraint stress-induced sensitization and (b) allodynia induced by inhalational umbellulone.
• To induce the injury-free migraine model, mice were submitted to three days of restraint stress, and tactile frequency of response was evaluated over the next two weeks.
• Fourteen days after the last restraint stress, mice were exposed to inhalational umbellulone oil (0.01M), for 30 min under isofluorane anesthesia (2%), followed by tactile response frequency assessment.