APE1/Ref-1 redox function contributes to inflammatory pain sensitization

We demonstrate that APE1 expression and subcellular distribution are significantly altered in rats at 4 days post CFA injection. We observed around 30% reduction in the overall APE1 mRNA and protein levels. Interestingly, our data point to an increased nuclear accumulation in the inflamed group as compared to the sham group. E3330 inhibitor injection in CFA rats normalized APE1 mRNA expression and changed its distribution toward cytosolic accumulation. Furthermore, intrathecal injection of E3330 decreased inflammation (i.e. reduced IL-6 expression) and alleviated pain, as assessed by measuring the paw withdrawal threshold with the von Frey test. In conclusion, our data indicate that changes in APE1 expression and sub-cellular distribution are implicated in inflammatory pain mechanisms mediated by APE1 redox functions. Further studies are required to elucidate the exact function of APE1 in inflammatory pain processes.