Activation of Proteinase-Activated Receptors Induces Itch-Associated Response Through Histamine-Dependent and -Independent Pathways in Mice

Proteinase-activated receptor-2 (PAR(2)) participates in itch, but the role of the other Subtypes of this receptor remain unknown. To investigate this issue, scratching, an itch-related behavior, was observed following intradermal injections of the activating peptides of PAR(1-4) In mice. Activating peptides of PAR(1), PAR(2), and PAR(4), but not PAR(3), induced scratching. The antihistamine terfenadine Suppressed scratching elicited by activating peptides of PAR, and PAR(4), but not PAR(2). These results suggest that PAR(1), PAR(2), and PAR(4) are involved in itch and that histamine is a cause of itch related to PAR(1) and PAR(4), but not PAR(2).