HDAC inhibitors restore C-fibre sensitivity in experimental neuropathic pain model

Background and PurposeHypoesthesia is a clinical feature of neuropathic pain. The feature is partly explained by the evidence of epigenetic repression of Na(v)1.8 sodium channel in the dorsal root ganglion (DRG). Experimental ApproachWe investigated the possibility of trichostatin A (TSA), valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA) to reverse the unique C-fibre sensitivity observed following partial ligation of sciatic nerve in mice. Key ResultsNerve injury-induced down-regulation of DRG Na(v)1.8 sodium channel and C-fibre-related hypoesthesia were reversed by TSA, VPA and SAHA treatments, which inhibit histone deacetylase (HDAC), and increase histone acetylation at the regulatory sequence of Na(v)1.8. Conclusions and ImplicationsTaken together, these studies provide the evidence that hypoesthesia and underlying down-regulation of Na(v)1.8, negative symptoms observed in nerve injury-induced neuropathic pain models are regulated by an epigenetic chromatin remodelling through HDAC-related machineries.