• Xuelong Zhou, Chenjing Zhang, Congjuan Zhang, Yunan Peng, Yin Wang, and Hongjiao Xu.
• From the Department of Anesthesiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China (X.Z.); Department of Gastroenterology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China (Chenjing Z.); Department of Digestive Endoscopy, Chuzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine, Chuzhou, China (Congjuan Z.); Department of Anesthesiology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China (Y.P.); Department of Anesthesiology, Taizhou People's Hospital, Taizhou, Jiangsu, China (Y.W.); and Department of Anesthesiology, the First People's Hospital of Shanghai Transportation University, Shanghai, China (H.X.).
• Anesthesiology. 2017 May 1; 126 (5): 967-977.

BackgroundThe authors and others have previously shown that the up-regulation of spinal ephrin type-b receptor 1 plays an essential role in the pathologic process of nerve injury-induced nociceptive hypersensitivity, but the regulatory mechanism remains unclear.MethodsRadiant heat and von Frey filaments were applied to assess nociceptive behaviors. Real-time quantitative polymerase chain reaction, Western blotting, fluorescence in situ hybridization, immunofluorescence, immunohistochemistry, dual-luciferase reporter gene assays, recombinant lentivirus, and small interfering RNA were used to characterize the likely mechanisms.ResultsPeriphery nerve injury induced by chronic constriction injury of the sciatic nerve significantly reduced spinal microRNA-182-5p (miR-182-5p) expression levels, which were inversely correlated with spinal ephrin type-b receptor 1 expression (R = 0.90; P < 0.05; n = 8). The overexpression of miR-182-5p in the spinal cord prevented and reversed the nociceptive behaviors induced by sciatic nerve injury, accompanied by a decreased expression of spinal ephrin type-b receptor 1 (recombinant lentiviruses containing pre-microRNA-182: 1.91 ± 0.34 vs. 1.24 ± 0.31, n = 4; miR-182-5p mimic: 2.90 ± 0.48 vs. 1.51 ± 0.25, n = 4). In contrast, the down-regulation of spinal miR-182-5p facilitated the nociceptive behaviors induced by sciatic nerve injury and increased the expression of spinal ephrin type-b receptor 1 (1.0 ± 0.26 vs. 1.74 ± 0.31, n = 4). Moreover, the down-regulation of miR-182-5p and up-regulation of ephrin type-b receptor 1 caused by sciatic nerve injury were mediated by the N-methyl-D-aspartate receptor.ConclusionsCollectively, our findings reveal that the spinal ephrin type-b receptor 1 is regulated by miR-182-5p in nerve injury-induced nociceptive hypersensitivity.

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