Pain Medicine  |   May 2017
MicroRNA-182-5p Regulates Nerve Injury–induced Nociceptive Hypersensitivity by Targeting Ephrin Type-b Receptor 1
Author Notes
  • 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.).
  • X.Z., Chenjing Zhang, and Congjuan Zhang contributed equally to the research project.
    X.Z., Chenjing Zhang, and Congjuan Zhang contributed equally to the research project.×
  • Submitted for publication July 21, 2016. Accepted for publication February 2, 2017.
    Submitted for publication July 21, 2016. Accepted for publication February 2, 2017.×
  • Address correspondence to Dr. Zhou: Department of Anesthesiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China. zhouxuelong0258@126.com. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Pain Medicine / Basic Science / Central and Peripheral Nervous Systems / Pain Medicine
Pain Medicine   |   May 2017
MicroRNA-182-5p Regulates Nerve Injury–induced Nociceptive Hypersensitivity by Targeting Ephrin Type-b Receptor 1
Anesthesiology 5 2017, Vol.126, 967-977. doi:10.1097/ALN.0000000000001588
Anesthesiology 5 2017, Vol.126, 967-977. doi:10.1097/ALN.0000000000001588
Abstract

Background: The 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.

Methods: Radiant 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.

Results: Periphery 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 (R2 = 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.

Conclusions: Collectively, our findings reveal that the spinal ephrin type-b receptor 1 is regulated by miR-182-5p in nerve injury–induced nociceptive hypersensitivity.