To develop agents for severe pruritus related to atopic dermatitis, we established an assay for evaluating pruritus using the frequency of scratching in mice as an index. In addition, we clarified the mechanism of pruritus using the assay, and investigated inhibitors from natural sources to clarify the mechanism by which they inhibit pruritus.
(1) We compared itching reactions between type I allergy model mice, in which sensitization with an antigen, and healthy mice. In the sensitized mice, platelet aggregation was significantly enhanced, and the blood coagulation time was shortened. Furthermore, PAF antagonists and blood coagulation system agonists inhibited or relieved pruritus. Therefore, we considered the mechanism involved in exacerbation of pruritus and chronic pruritus in blood-mediated conditions, and suggested the possibility of agents for pruritus with a new action mechanism.
(2) We compared the inhibitory effects of various inhibitors on pruritus between a chronic pruritus mo
del, in which marked chronic scratching in atopic dermatitis model NC mice, and a transient pruritus model, in which administration of a pruritus-inducing substance to normal mice induced scratching activities. We investigated pruritus-associated substances in the two models. As a result, central-inhibiting agents effectively inhibited pruritus in the chronic pruritus model, differing from those in the transient pruritus model. Therefore, we consider that an assay for investigating not only peripheral but also central pruritus inhibitors must be established. Currently, this trial is in progress. In addition, the possibility of new agents for pruritus was suggested, as we obtained the finding that antagonists against 5HT_3, a pain receptor, are also involved in pruritus.
(3) Using several established assays, we clarified the anti-pruritus activity of several natural sources, isolated active compounds from the natural sources, analyzed the structures of them, and investigated the action mechanism to develop new agents for pruritus. Less