Figure 1

Application of IL-6 to the dura elicited cutaneous allodynia via activation of the MEK/ERK pathway. (A) Withdrawal thresholds to tactile stimuli applied to the face and the hind-paws were measured in rats before and immediately after dural application of 1 ng IL-6 (n = 16) or SIF (n = 17). For both facial and hind-paw responses, two-factor analysis of variance indicated that response thresholds of IL-6-treated rats were significantly (p < 0.0001) less than those of SIF-treated rats. (B) Rats received dural administration of SIF (white bar, n = 17), 0.1 ng IL-6 (gray bar, n = 22) or 1 ng IL-6 (black bar, n = 16). Withdrawal thresholds to tactile stimuli were measured for 5 h and data were converted to area over the time-effect curve. IL-6 dose-dependently decreased the withdrawal threshold both in the face and in the hind-paw. Significant (*p < 0.05, **p < 0.01) differences among means for each group were determined by analysis of variance followed by Newman-Keuls post hoc test. (C) Application of 1 ng IL-6 was given with vehicle (white bars, 1% DMSO, n = 12) or with U0126 (black bars, 1 nmol, n = 12). Withdrawal thresholds to tactile stimuli were measured for 5 h and data were converted to area over the time-effect curve and normalized as a percentage of the IL-6-treated group. Coapplication of U0126 significantly abolished behavioral signs of tactile allodynia of the face and hind-paw (*p < 0.05, **p < 0.01).