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

Figure 2

T-5224, Mino, and LAA ameliorated mechanical allodynia, inflammatory pain, and IL-6 induced hyperalgesia in rats. (a) Line plots indicate the effects of T-5224 (c-Fos/AP-1 inhibitor, 500 μg/50 μL), minocycline (Mino, 100 μg/50 μL), and L-2-aminoadipic acid (LAA, 1 mg/50 μL) on ipsilateral paw withdrawal mechanical thresholds (PWMTs) in FCA-induced inflammatory pain. versus control. ^# versus FCA; one-way ANOVA with Bonferroni tests. (b) ROC curves and AUC of T-5224, Mino, and LAA on the ipsilateral side of FCA-treated rats. (c) Intrathecal injection of T-5224, Mino, and LAA did not alter FCA-induced mechanical nociception on the contralateral noninflamed side (). (d, f) Interleukin-6 (20 ng/50 μL) microinjection reversed T-5224-induced mechanical hyperalgesia (500 μg/50 μL), Mino (100 μg/50 μL), and LAA (1 mg/50 μL) in the right and left hind paws of naïve rats; versus control. ^# versus IL-6, one-way ANOVA with Bonferroni tests. (e) ROC curves and AUC for T-5224, Mino, and LAA in the right hind paws of naïve rats. Data are shown as (). AUC: area under receiver operator characteristic curves; ROC: receiver operator characteristic curve.

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