Putative mechanism of the itch–scratch circle: Repeated scratching decreases the cutaneous level of prostaglandin D 2, a mediator that inhibits itching

Abstract

In atopic dermatitis, scratching of the skin as a reaction to itching causes injury to the skin, which, in turn, further increases the itching resulting in the establishment of the so-called itch–scratch circle. We have shown that prostaglandin (PG) D 2 plays an inhibitory role against pruritus in mice with atopic-like dermatitis; therefore, we examined the relationship between scratching and the cutaneous PGD 2 level using an artificial scratching model with a wire brush. Mechanical scratching induced a temporary increase of the skin PGs levels (PGE 2, PGD 2, 6-ketoPGF 1 α , PGF 2 α ). The skin PGD 2 level and the ability of PGD 2 production decreased at 48 h after repeated scratch, compared to that of normal skin, not so after single scratch. Immunohistochemical analysis and Western blotting revealed a decrease in the levels of cyclooxygenase-1 (COX-1) and hematopoietic PGD synthase in mechanically scratched skin. The reduced ability of the skin for PGD 2 production following mechanical scratching could be caused by this decrease in the expression levels of COX-1 and PGD 2 synthase. The results suggest that repeated scratching in mice decreases the ability of the skin to produce PGD 2, which is an endogenous mediator that inhibits pruritus, resulting in the establishment of the itch–scratch circle.