The Role Of Hypomethylation Of NGF Promoter Regions In The Functional Regulation Of Inflammatory Hyperalgesia

Background:Chronic pain is usually accompanied by tissue damage and inflammation.However,the pathogenesis of chronic pain remains unclear.Methods:We investigated the role of nerve growth factor(NGF)in the chronic inflammatory pain induced by complete Freund's adjuvant(CFA),explored the methylation status of CpG islands in the promoter regions of the NGF genes,and clarified the function and mechanism of C/EBP?-NGF signaling pathway from epigenetic perspective in the chronic inflammatory pain model.Results:CFA induced significant hyperalgesia and continuous upregulation of NGF mRNA and protein levels in the L4-6 dorsal root ganglions(DRGs)in rats.Hypomethylation of CpG islands occurred in the NGF gene promoter region after CFA treatment.At the same time,the miR-29b expression level was significantly increased,while the DNA methyltransferase 3b(DNMT3b)level reduced significantly.Moreover,CFA treatment promoted binding of C/EBPa to the NGF gene promoter region and C/EBP? siRNA treatment obviously decreased expression of NGF levels and also alleviate inflammatory hyperalgesia significantly in rats.Conclusion:Collectively,the results indicated that CFA leads to the upregulation of miR-29b level,which represses the expression of DNMT3b,enhances the demethylation of the NGF gene promoter regions,and promotes the binding of C/EBPa with the NGF gene promoter,thus results in the upregulation of NGF gene expression and maintenance of chronic inflammatory pain.