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Emerging reports demonstrated that Wnt/β-catenin pathways critically contributed to the induction and maintenance of chronic pain induced by peripheral inflammation and nerve injury.Emerging evidences also suggested the critical role of epigenetic mechanism in the setting of chronic pain.The present study aims to elucidate the potential epigenetic mechanism underlying the altered Wnt signaling and its functional significance in the rats with neuropathic pain induced by chronic constriction injury(CCI)in sciatic nerve.In the present study significantly increased expression of Wnt3a was observed in the dorsal horn of the rats with CCI.It was also found that significantly increased histone H3 acetylation and decreased cytosine methylation in the promoter region of Wnt3a in the dorsal horn of the rats with CCI.Intrathecal application of XAV939,an inhibitor of Wnt signaling,significantly decreased the expression of the active β-catenin and attenuated the painful behavioral response to thermal and mechanical stimuli in the rat with CCI.These results demonstrated an epigenetic upregulation of Wnt3a in the dorsal horn,which critically contributed to the maintenance of painful behavior in the rats with neuropathic pain.