title: miR23b ameliorates neuropathic pain in spinal cord by silencing NADPH oxidase 4.
abstract: OBJECTIVE
  Neuropathic pain is a well-known type of chronic pain caused by damage to the nervous system. Until recently, researchers have been primarily focused on identifying the cellular or chemical sources of neuropathic pain or have approached neuropathic pain via the basis of biological study. We investigated whether mmu-mir-23b (miR23b) infusion can alleviate pain by compensating for the abnormally downregulated miR23b by reducing the expression of its target gene, NADPH oxidase 4 (NOX4), a reactive oxygen species (ROS) family member overexpressed in neuropathic pain.
  
  
  RESULTS
  Ectopic miR23b expression effectively downregulated NOX4 and was normalized to GAD65/67 expression. Moreover, the animals with neuropathic pain showed significant improvements in the paw withdrawal thresholds following miR23b infusion. Normalizing miR23b expression in tissue lesions caused by neuropathic pain induction reduced inflammatory mediator expression and increased the level of several ROS scavengers. Moreover, GABAergic neurons coexpressed suboptimal levels of miR23b and elevated NOX4/ROS after pain induction at the cellular level. MiR23b protects GABAergic neurons against ROS/p38/JNK-mediated apoptotic death. By evaluating the functional behavior of the mice receiving pain/miR23b, normal/anti-miR23b, or anti-miR23b/si-NOX4, the positive role of miR23b and the negative role of NOX4 in neuropathic pain were confirmed.
  
  
  CONCLUSIONS
  Based on this study, we conclude that miR23b plays a crucial role in the amelioration of neuropathic pain in the injured spinal cord by inactivating its target gene, NOX4, and protecting GABAergic neurons from cell death. We finally suggest that miR23b may provide attractive diagnostic and therapeutic resources for effective pain modulation in neuropathic pain.
authors.affiliation: Laboratory of Stem Cell Biology, Department of Biotechnology, College of Veterinary Medicine, Seoul National University, Seoul, Korea.
authors.forename: Young Bin
authors.initials: YB
authors.lastname: Im
authors.forename: Min Ki
authors.initials: MK
authors.lastname: Jee
authors.forename: Jin Sun
authors.initials: JS
authors.lastname: Jung
authors.forename: Jee In
authors.initials: JI
authors.lastname: Choi
authors.forename: Jin Hwa
authors.initials: JH
authors.lastname: Jang
authors.forename: Soo Kyung
authors.initials: SK
authors.lastname: Kang
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D004195:Disease Models, Animal; D005260:Female; D020868:Gene Silencing; D051379:Mice; D035683:MicroRNAs / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000235:genetics*; D009437:Neuralgia / Q000235:genetics* / Q000628:therapy; D013116:Spinal Cord / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; C534062:Mirn23b microRNA, mouse; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C422943:Nox4 protein, mouse