KOR agonist (U50488) directly blocked PGE
-induced inflammatory hyperalgesia in rats and mice. (A) Mechanical hyperalgesia in rats was induced by an ipl. injection of PGE2 (100 ng/paw). After 2 h, U50488 (3-30 μg/paw) was administrated into the ipsilateral or contralateral (CL) paws. Mechanical hyperalgesia was evaluated 1 h after U50488 injection using the electronic von Frey test. (B) The antinociceptive effect of a local injection of U50488 (10 μg/paw, 2 h after PGE2 injection) upon PGE2-induced hyperalgesia was prevented by treatment with a selective antagonist of KOR (Nor-BNI; 30 min before U50488 injection) (C-D) Mechanical hyperalgesia was induced by an ipl. injection of PGE2 (30 ng/paw) in mice. After 30 min, U50488 (1-9 μg/paw) was administrated into the ipsilateral or contralateral (CL) paws. Data are expressed as the mean ± S.E.M. of 5-6 animals per group. * Indicates statistical significance compared to the saline group. # Indicates statistical significance compared to the PGE2 control group. P < 0.05, one-way ANOVA, followed by the Bonferroni correction.