Phosphorylation at Ser 727 Increases STAT3 Interaction with PKCε Regulating Neuron–Glia Crosstalk via IL-6-Mediated Hyperalgesia In Vivo and In Vitro

Figure 4

Evaluation of paw withdrawal mechanical threshold (PWMT) in rats with inflammatory pain and IL-6-induced hyperalgesia after the administration of PKCε inhibitor peptide, APTSTAT3-9R (STAT3 inhibitor), or anti-IL-6 antibody. (a) Anti-IL-6 antibody (100 ng/50 μL) rapidly attenuated FCA-induced pain for several days on the ipsilateral inflamed side. PKCε inhibitor peptide (100 μg/50 μL) and APTSTAT3-9R (20 μg/50 μL) exerted antinociceptive effects 24 h after drug injection. versus control. ^# versus FCA, one-way ANOVA followed by Bonferroni tests. (b) ROC curves and AUC of PKCε inhibitor peptide, APTSTAT3-9R, and anti-IL-6 on the ipsilateral side of FCA-treated rats. (c) None of the PKCε inhibitor peptide, APTSTAT3-9R, and anti-IL-6 affected contralateral mechanical paw withdrawal thresholds in rats with FCA-induced inflammatory pain. (d, f) Interleukin-6 (20 ng/50 μL) microinjected 10 min after naïve rats were injected with PKCε inhibitor peptide (100 μg/50 μL) or APTSTAT3-9R (20 μg/50 μL) did not affect IL-6-induced mechanical hyperalgesia, whereas anti-IL-6 antibody (100 ng/50 μL) did. versus control. ^# versus IL-6, one-way ANOVA followed by Bonferroni tests. (e) ROC curves and AUC of PKCε inhibitor peptide, APTSTAT3-9R, and anti-IL-6 in the right hind paws of naïve rats. Data are shown as (). AUC: area under receiver operating characteristic curve; ROC: receiver operator characteristics curve.

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