miRNA Expression Change in Dorsal Root Ganglia After Peripheral Nerve Injury.

Chang, Hsueh-Ling; Wang, Hung-Chen; Chunag, Yi-Ta; Chou, Chao-Wen; Lin, I-Ling; Lai, Chung-Sheng; Chang, Lin-Li; Cheng, Kuang-I

The role of microRNAs (miRNAs) in the regulation of nerve injury-induced neuropathic pain is unclear. The aims of this study were to assess and compare miRNA expression profiles in dorsal root ganglia (DRG) following three different kinds of peripheral nerve injury, including spinal nerve ligation (SNL), dorsal root transection (DRT), and ventral root transection (VRT), in Sprague-Dawley rats. Responses to thermal and mechanical stimuli were measured preoperatively and on postoperative days (PODs) 1, 4, and 7. A miRNA microarray analysis was used to detect the miRNA expression profiles in injured L5 DRG from SNL, DRT, and VRT on POD 7. Validation of miRNA expression was performed by qPCR and in situ hybridization. Rats receiving SNL displayed significantly higher mechanical hypersensitivity, but those receiving DRT developed higher thermal hypersensitivity. The number of miRNAs that were significantly upregulated in L5 DRG was 49 (7.2%), 25 (3.7%), and 146 (21.5%) following SNL, DRT, and VRT, respectively. On the other hand, 35 (5.1%) miRNAs were significantly downregulated in the SNL group, 21 (3.1%) miRNAs in the DRT group, and 41 (6.0%) miRNAs in the VRT group. Of the four miRNAs that were mutually aberrant in all three models, two were significantly upregulated (twofold), miR-21 and miR-31, and two were significantly downregulated, miR-668 and miR-672. Using in situ hybridization, miRNA-21, miRNA-31, miRNA-668, and miRNA-672 were found to localize to neurons in the DRG. Collectively, the mutual abnormal miRNA expression of miR-21, miR-31, miR-668, and miR-677 implied that these miRNAs may be therapeutic targets for alleviating multiple forms of neuropathic pain.