Effects of topical application of tacrolimus on acute itch-associated responses in mice

Using mice, we examined whether the topical application of tacrolimus would produce an acute anti-pruritic effect. An itch-related response, scratching, was elicited by intradermal injections of mosquito allergen (10 mu g/site) in sensitized mice and SLIGRL-NH2 (Protease-activated receptor-2 agonist, 50 nmol/site), histamine (100 nmol/site), serotonin (100 nmol/site) and substance P (100 nmol/site) in naive ones. Topical application of 1%, but neither 0.1% nor 0.3%, tacrolimus to the skin I h before injection inhibited scratching induced by mosquito allergen and SLIGRL-NH2, without effects on scratching induced by histamine, serotonin, and substance P. Topical tacrolimus also inhibited licking induced by an intraplantar injection of capsaicin (0.1 mu g/site). These results suggest that topical tacrolimus exerts acute inhibitory effects on allergic and protease-activated receptor-2-mediated itching. Though precise mechanisms remain unclear, the action on sensory neurons expressing protease-activated receptor-2 and transient receptor potential vanilloid-1 capsaicin receptor may be involved in the inhibitory effects of tacrolimus.