AKT mediates the peripheral antinociceptive action of a KOR agonist. (A) Mechanical hyperalgesia in rats was induced by an ipl. injection of PGE2 (100 ng/paw). The antinociceptive effect of U50488 (10 μg/paw, 2 h after PGE2 injection) after PGE2-induced hyperalgesia was prevented by treatment of the rat paw with a selective inhibitor of AKT (AKT inhibitor IV- 10 μg/paw, 30 min before U50488 injection). Data are expressed as the mean ± S.E.M. of 5-6 animals per group. * Indicates statistical significance compared to the vehicle group. # Indicates statistical significance compared to the U50488 treated group. P < 0.05, one-way ANOVA, followed by the Bonferroni correction. * P < 0.05, compared with vehicle treatment. (B) In vitro stimulation of DRG primary culture neurons from rats with U50488 (100 nM) increased the phosphorylation of AKT analyzed by Western blot. (C) Pre-incubation (10 min) with vehicle, wortmannin (WTT - 100 nM), AS605240 (100 nM) or naloxone (NLX- 1 μM) reduced U50488-induced AKT phosphorylation.