P2X4 receptor (P2X4R) can be up-regulated after nerve injury and its mediated spinal microglial activation makes a critical contribution to pathologically enhanced pain processing in the dorsal horn. Although some studies have partly clarified the mechanism underlying altered P2X4R expression, the specific mechanism is not well understood. MicroRNAs (miRNAs) are small noncoding RNAs, which control gene expression by binding with their target mRNAs. Thus, in the present study, whether miRNA was

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... nvolved in pathogenesis of neuropathic pain by regulating the P2X4R was investigated. Our results showed that P2X4R was up-regulated in the spinal dorsal horn of mice following spared nerve injury (SNI), and 69 miRNAs (46 up-regulated and 23 down-regulated miRNAs) were differently expressed (fold change > 2.0, P < 0.05). P2X4R was a major target of miR-106b-5p (one of down-regulated miRNAs) with bioinformatics technology and quantitative real time PCR analysis validated the expressed change of miR-106b-5p, dual-luciferase reporter assays confirmed the correlation between them. Fluorescence in situ hybridization was used to show cell co-localization of P2X4R and miR-106b-5p in the spinal dorsal horn. Transfection with miR-106b-5p mimic into BV2 cells reversed the up-regulation of P2X4R induced by LPS. Moreover, miR-106b-5p overexpression significantly attenuated neuropathic pain induced by SNI with decreased expression of P2X4R mRNA and protein in the spinal dorsal horn, intrathecal miR-106b-5p antagomir induced pain behaviors and increased the expression of P2X4R in the spinal dorsal horn of naïve mice. These data suggest that miR-106b-5p can serve as an important regulator of neuropathic pain development by targeting P2X4R.