Vol. 286, Issue 3, 1140-1145, September 1998

Substance P Induction of Itch-Associated Response Mediated by Cutaneous NK₁ Tachykinin Receptors in Mice¹

Tsugunobu Andoh, Tetsuro Nagasawa, Masamichi Satoh and Yasushi Kuraishi

Department of Applied Pharmacology, Faculty of Pharmaceutical Sciences (T.A., Y.K.), Department of Clinical Application (T.N.), Research Institute for Wakan-yaku, Toyama Medical & Pharmaceutical University, Toyama; and Department of Molecular Pharmacology (M.S.), Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan

Our experiments were conducted to determine whether substance P (SP) would elicit an itch sensation mediated by mast cells in mice. An intradermal injection of SP (10-135 µg site¹) into the rostral back of the ICR mouse dose-dependently produced scratching of the injected site. The SP- (135 µg site¹ = 100 nmol site¹) induced scratching was inhibited by capsaicin (repeated administration) and naloxone; features being similar to itch in humans. SP elicited scratching in mast cell-deficient (WBB6F1 W/W^v) mice as well as control (+/+) mice. Pretreatment with compound 48/80 produced similar degrees of inhibition of SP-induced scratching in mast cell-deficient mice as well as control +/+ and ICR mice. Intradermal injections of the NK₁ receptor agonist GR73632 produced dose-dependent scratching, while the NK₂ agonist GR64349 and the NK₃ agonist senktide were without effects. SP-induced scratching was inhibited by the NK₁ receptor antagonists spantide and L-668,169, but not by the NK₂ antagonist L-659,877. The results suggest that scratching of the mouse induced by an i.d. injection of SP is itch-associated response. The SP action may be mediated at least partly by cutaneous NK₁ receptors, and mast cells may not be key factors in SP-induced itching.