IL-6 promoted ERK-dependent hyperexcitability of dural afferents in response to ramp current stimuli. (A) Action potentials were elicited by 1 s ramp current injection ranging from 0.1 to 0.7 nA in 0.2 nA increments from resting membrane potential. Dural afferents treated with IL-6 showed increased numbers of action potentials and shorter time-to-first action potential (AP) peak compared with vehicle-treated dural afferents. IL-6-induced hyperexcitability was blocked by pretreatment with 10 μM U0126. (B) Difference in the mean numbers of action potentials among groups was analyzed by comparing the slopes and intercepts generated from linear regression. Comparison among several groups for time-to-first spike was performed by two-factor analysis of variance. Dural afferents treated with 50 ng/ml IL-6 (red square, n = 16) showed a significant (p < 0.05) increase in number of action potentials and a significant decrease in time-to-first peak compared with vehicle-treated dural afferents (black circle, n = 12). Pretreatment with 10 μM U0126 (blue triangle, n = 13) for 10 mins significantly reversed IL-6-induced hyperexcitability.
Yan et al. Molecular Pain 2012 8:6 doi:10.1186/1744-8069-8-6