Intraplantar injection of IL-6 or coinjection of IL-6 and NGF into the hindpaw of mice induces long-lasting mechanical allodynia blocked by cotreatment with anisomycin, U0126, or 4EGI1. Mechanical thresholds were measured at the indicated time points before and after intraplantar injection (indicated by downward arrows). A, IL-6 (0.1 ng) induced a significant decrease in withdrawal thresholds that was blocked by coinjection of the general protein synthesis inhibitor anisomycin (25 μg). B, IL-6 (0.1 ng)-induced decreases in withdrawal thresholds were blocked by coinjection of the MEK inhibitor U0126 (10 μg). C, D, IL-6 (0.1 ng)-mediated allodynia was blocked with the inhibitor of eIF4F complex formation, 4EGI1 (2.5, 10, and 25 μg) in a dose-dependent manner. E, F, Coinjection of IL-6 (0.1 ng) and NGF [0.02 (E) and 50 (F) ng] resulted in a significant decrease in the mechanical thresholds at the indicated time points, and these effects were blocked by coinjection of 4EGI1 (25 μg). G, Coinjection of the transcription inhibitor actinomycin D (300 ng) had no effect on IL-6 (0.1 ng)-mediated allodynia. *p < 0.05, **p < 0.01, ***p < 0.001.