The Effects Of Chronic Pain On The Expression Of MicroRNA In The Nervous System

Introduction:Chronic pain has become a major health problem, most of which always accompany with some pathological changes in nervous system that were resulted from changes of genes expression. MicroRNAs (miRNAs) are small noncoding RNAs of19-24nt and are involved in gene expression regulation. They are associated with cell proliferation, differentiation, apoptosis, and carcinogenesis. The specific expression profiles of miRNAs have been found in many diseases, but there are few studies on chronic pain.Objective:We’d like to investigate the differently expressed miRNAs through miRNA microarray, and predict their target genes in the spinal dorsal horn of chronic pain rats, as is useful for further study of miRNA in chronic pain and provides probable targets for the therapy of chronic pain.Methods:Forty male SD rats were randomly devided into five groups (n=8):Naive group, Sham group, CCI(Chronic Constrictive Injury) group, CFA(Complete Freud Adjuvant) group and NS group. Both the CCI model and CFA model were established. MicroRNA microarray was used to investigate the differently expressed miRNAs in CCI rats, and the selected miRNAs were confirmed by real time reverse transcriptional polymerase chain reaction (RT-PCR). These miRNAs were also tested in CFA rats by real time RT-PCR. Furthermore, we predicted the possible target genes by anticipated algorithms of three databases.Result:The mechanical and thermal hyperalgesic thresholds of CCI and CFA rats were decreased significantly (P<0.05), as means chronic pain models were established successfully. MiRNA microarray showed that the expression of miR-99b was up-regulated, while the expression of miR-34b, miR-325-5p, miR-349, miR-674-3p and miR-879was down-regulated in spinal dorsal horn of CCI rats compared with sham and naive rats. The different expression of four miRNAs was confirmed by quantitative RT-PCR. The miR-99b was up-regulated and miR-674-3p was down-regulated in CFA rats. Target genes of the miRNAs were found out by three databases.Conclusion:The differently expressed miRNAs in CCI and CFA rats were discovered. These informations may provide some candidate miRNAs for further confirming their roles in the mechanism of chronic pain. Accordingly, miRNAs may become the potential therapeutic targets for treating chronic pain.