Figure 12.

Changes in PKA signaling contribute to the prolongation of PGE₂-induced hyperalgesia in type II priming. A, Rats received 3 hourly intradermal injections of vehicle or DAMGO (1 μg) on the dorsum of the hindpaw. 8-bromo cAMP (1 μg) was injected at the same site 1 h later and mechanical hyperalgesia was evaluated after 30 min and 4 h. 8-bromo cAMP produced mechanical hyperalgesia in both groups at 30 min. However, in the group previously treated with DAMGO, it was significantly enhanced and prolonged and still present after 4 h, as opposed to the vehicle-treated group (F_(1,20) = 96.82; ***p < 0.0001, when comparing both groups; two-way repeated-measures ANOVA followed by Bonferroni post hoc test), suggesting an increased activation of PKA signaling by repeated MOR activation; B, Rats received 3 hourly intradermal injections of DAMGO (1 μg) on the dorsum of the hindpaw and a fourth injection of 8-bromo cAMP (1 μg) at the same site. Significant mechanical hyperalgesia was observed 30 min later. Injection of H-89 (1 μg) 1 h after 8-bromo cAMP inhibited the ongoing hyperalgesia evaluated 3 h later that was produced by the previous treatment with repeated injections of DAMGO (NS, p > 0.05 vs baseline; one-way repeated-measures ANOVA followed by Bonferroni post hoc test), indicating a role of PKA in the increased activation of the cAMP signaling pathway produced by repeated MOR agonist administration. n = 6 paws per group.