Pruritus-associated response mediated by cutaneous histamine H₃ receptors

Background: Histamine is one of the most common chemical mediators causing pruritus, and H₁ receptor antagonists have been used as a first choice in its treatment. On the other hand, although the presence of H ₃ receptors has been identified in the skin, few studies have investigated the involvement of H₃ receptors on pruritus. Objective: The purpose of this study was to examine whether H₃ receptor agonist or antagonist influences the incidence of scratching behaviour in ICR or mast cell-deficient WBB6F₁-W/W^v mice. Methods: The mice were given an intradermal injection of H₃ receptor agonist or antagonist into the rostral part of the back, and the occurrence of scratching behaviour at the injected site by the hind paws was counted over 60 min. Results: H ₃ receptor antagonists, thioperamide and AQO145 significantly increased the incidence of scratching behaviour in ICR mice. H₃ receptor agonist, (R)-alpha-methylhistamine, had no effect. On the other hand, (R)-alpha-methylhistamine significantly inhibited thioperamide or AQO145-induced scratching behaviour. In addition, both thioperamide and AQ0145 elicited scratching behaviour in mast cell-deficient WBB6F₁-W/W ^v mice. Conclusion: From these results, it may be concluded that H₃ receptors are involved in the modulation of pruritus in the skin, and mast cells are not essential in this response. In addition, H₃ receptor agonists can be useful as a novel therapeutic approach against pruritus.