Figure 1

Lack of involvement of CaMKIIα or MAPK in persistent sensitization. A) IL-6 was injected into the left hindpaw (i.pl.) of mice and myr-CamKIINTide (peptide CaMKIIα inhibitor) or the non-myristolyated control were injected i.t. at the same time testing the initiation of persistent sensitization. Hindpaw mechanical thresholds were measured at indicated time points. Myr-CamKIINTide inhibited allodynia induced by IL-6 injection (left) and attenuated PGE₂-precipitated persistent sensitization (right). B) On the other hand, Myr-CamKIINTide administered i.t. on day 4 after IL-6 injection had no effect on PGE₂-precipitated persistent sensitization. C) Likewise, no effect was observed in the same experimental paradigm with the small molecule CaMKIIα inhibitor KN93. D) IL-6 was injected i.pl. and the MEK inhibitor U0126 or VEH control were injected i.t. at the same time testing the initiation of persistent sensitization. U0126 inhibited allodynia induced by IL-6 injection (left) and attenuated PGE₂-precipitated persistent sensitization (right). E) However, U0126 given i.t. 4 days after IL-6 had no effect on PGE₂-precipitated persistent sensitization. All experiments N = 6. * p < 0.05, ** p < 0.01, *** p < 0.001, two way ANOVA with Bonferroni post hoc test.