CFA- or carrageenan-induced mechanical hyperalgesia requires PKA and PKCε activity.

<p>(A) Dosage curve for protein kinase A (PKA) and protein kinase Cε (PKCε) inhibitors. Mice received intraplantar injection with 25 μl of different doses of PKA inhibitor (PKAI, H89) before 50% CFA injection or PKCε inhibitor (PKCεI, TAT-PKCεV_1-2) or control peptide (ctrl50) at 4 h after CFA injection. The PWT on ipsilateral side was measured at 90 min after the second injection. Data are mean±SEM of total tested mice (n = 6–12 per group). ##p<0.01, ###p<0.001 compared to PKAI/CFA with CFA only group and ***p<0.001 compared to PKCεI/CFA with CFA only group by one-way ANOVA with a post-hoc Bonferroni test. (B, C) Mice were injected with PKAI (50μM) or PKCεI (50μM) before (0 h) or after (3, 4, 5 h or 1 or 16 days) CFA injection. The PWT on the ipsilateral side (B) or contralateral side (C) was measured at 90 min after the second injection. Data are mean±SEM of total tested mice (n = 6 per group). ###***p<0.001 compared to CFA-injected groups by two-way ANOVA with a post-hoc Bonferroni test. (D) Mice were injected with PKAI (50μM) or PKCεI (50μM) before (0 h) or after (3, 4, 5 h or 1 or 10 days) carrageenan injection. The PWT on the ipsilateral side was measured at 90 min after the second injection. Data are mean±SEM of total tested mice (n = 6 per group). ###***p<0.001 compared to carrageenan-injected groups by two-way ANOVA with a post-hoc Bonferroni test.