Repeated treatment with the traditional medicine Unsei-in inhibits substance P-induced itch-associated responses through downregulation of the expression of nitric oxide synthase 1 in mice.

Unsei-in inhibits substance P (SP)-induced scratching of mice after repeated administration. The involvement of cutaneous nitric oxide (NO) in the SP-induced scratching led us to investigate the effects of Unsei-in on the cutaneous NO system in mice. Seven-day oral administration of Unsei-in (300, but not 100, mg/kg daily) significantly inhibited scratching and the increase of cutaneous NO after intradermal SP injection. The NO synthase 1 (NOS1) inhibitor 7-nitroindazole (1 nmol/site) decreased SP-induced scratching and NO production. Repeated administration of Unsei-in (300 mg/kg) reduced the cutaneous NOS1 level. The results suggest that the inhibition of cutaneous NOS1 expression and NO production participates in the antipruritic action of Unsei-in.

Inhibitory effect of the repeated treatment with Unsei-in on substance P-induced itch-associated responses through the downregulation of the expression of NK(1) tachykinin receptor in mice.

Unsei-in, a traditional medicine, is prescribed against pruritic cutaneous diseases, but the mechanisms of antipruritic action are still unknown. In the present study, we examined the antipruritic effects of Unsei-in in mice. Single administration of Unsei-in did not inhibit substance P-induced itch-associated response (scratching) in mice. However, repeated treatment with Unsei-in for 7 d significantly inhibited substance P-induced scratching. The same repeated treatment with Unsei-in suppressed the expression of NK(1) tachykinin receptors in the skin. These results suggest that Unsei-in inhibits substance P-associated itching and that the inhibition is at least partly due to the suppression of the expression of NK(1) tachykinin receptors in the skin.