Effects of analgesics on bradykinin-induced writhing in mice presensitized with PGE2.

The intraperitoneal injection of 1 mg/kg PGE2 (which by itself was inactive) enhanced the writhing response induced by a subnociceptive dose of bradykinin (BK, 0.5 mg/kg ip) in male mice. The BK1 agonist, DesArg9-BK and the BK1 antagonist DesArg9-Leu8-BK did not affect writhing. The BK2 agonists, Lys-BK and Tyr-BK, like BK, induced writhing in the PGE2-treated mice. On the other hand, the DPhe7-analogs of BK, which antagonize BK at the BK2 subtype of receptors, potently inhibited the writhing response induced by BK. The writhing was also inhibited by morphine, but in contrast, non-steroidal antiinflammatory drugs (NSAIDs) only weakly inhibited the writhing response in this assay, suggesting that the nociceptive effect of BK was not significantly dependent upon the biosynthesis of PGE2. These results suggest that the algesic effect of BK in this mouse model is mediated via a BK2 receptor subtype.