Bradykinin-evoked scratching responses in complete Freund's adjuvant-inflamed skin through activation of B1 receptor

Abstract

Capsaicin, a potent algogen, induces an itch-related behavior in the presence of inflammation. In this study, we tested whether bradykinin (BK) can evoke a similar response and investigated the potential mechanisms involved in this process. Local inflammation was induced by intradermal injection of complete Freund's adjuvant (CFA) into the back of the neck, left hind foot or left cheek of male C57BL/6J mice. BK was then injected intradermally into the same area on indicated days. Four days after CFA inflammation, BK treatment evoked scratching responses in a time- and dose-dependent manner. For BK receptor antagonist treatment, inflamed-mice were either given an intraperitoneal injection of B(1) receptor (B(1)R) or B(2) receptor (B(2)R) antagonist 30 min prior to BK administration, or an intradermal co-injection of antagonist and BK into the inflamed area. Our results indicate that B(1)R and B(2)R act in an opposite fashion during this process, as pretreatment with B(1)R antagonist by intraperitoneal injection significantly reduced BK-induced scratching behavior, whereas B(2)R antagonist treatment dramatically increased scratching behavior. Moreover, combined injection of BK and B(2)R antagonist enhanced BK-induced scratching activity in CFA-inflamed mice. In addition, pretreatment or co-injection with B(2)R antagonist dramatically reduced the pain-related licking behavior induced by BK injection. The data suggest that BK-induced scratching responses in CFA-inflamed mouse skin occur via activation of B(1)R. Furthermore, B(1) and B(2) receptors play different roles in modulating BK-induced itch-related behavior in CFA-inflamed mice.