title: Intrathecal miR-183 delivery suppresses mechanical allodynia in mononeuropathic rats.
abstract: Members of the miR-183 family are unique in that they are highly abundant in sensory organs. In a recent study, significant downregulation was observed for miR-96 and miR-183 in the L5 dorsal root ganglion (DRG) 2 weeks after spinal nerve ligation (SNL). In this study, we focused on miR-183, which is the most regulated member of the miR-183 family, to look at the specific role on neuropathic pain. Persistent mechanical allodynia was induced with the L5 SNL model in 8-week-old male Sprague-Dawley rats. Paw withdrawal thresholds in response to mechanical stimuli were assessed with Von Frey filaments. Expression of miR-183 in the L5 DRG was assessed with quantitative real-time polymerase chain reaction (qPCR) analysis. Lentivirions expressing miR-183 were injected intrathecally into SNL rats. Changes in mechanical allodynia were assessed with Von Frey filaments. In addition, changes in the predicted target genes of miR-183 were assessed with qPCR. L5 SNL produced marked mechanical allodynia in the ipsilateral hindpaws of adult rats, beginning at postoperative day 1 and continuing to day 14. L5 SNL caused significant downregulation of miR-183 in adult DRG cells. Intrathecal administration of lentivirions expressing miR-183 downregulated SNL-induced increases in the expression of Nav1.3 and brain-derived neurotrophic factor (BDNF), which correlated with the significant attenuation of SNL-induced mechanical allodynia. Our results show that SNL-induced mechanical allodynia is significantly correlated with the decreased expression of miR-183 in DRG cells. Replacement of miR-183 downregulates SNL-induced increases in Nav1.3 and BDNF expression, and attenuates SNL-induced mechanical allodynia.
authors.affiliation: Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, No. 123 Dapi Rd, Kaohsiung, 833, Taiwan; Department of Anesthesiology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Chung-Ren
authors.initials: CR
authors.lastname: Lin
authors.forename: Kuan-Hung
authors.initials: KH
authors.lastname: Chen
authors.forename: Chien-Hui
authors.initials: CH
authors.lastname: Yang
authors.forename: Hui-Wen
authors.initials: HW
authors.lastname: Huang
authors.forename: Shyr-Ming
authors.initials: SM
authors.lastname: Sheen-Chen
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D005727:Ganglia, Spinal / Q000503:physiopathology*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006930:Hyperalgesia / Q000503:physiopathology*; D016086:Lentivirus / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D062552:NAV1.3 Voltage-Gated Sodium Channel / Q000378:metabolism; D009437:Neuralgia / Q000503:physiopathology; D017288:Pain Threshold / Q000502:physiology; D010812:Physical Stimulation; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D013127:Spinal Nerves / Q000293:injuries; D014110:Touch
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C584645:MIRN183 microRNA, rat; D035683:MicroRNAs; D062552:NAV1.3 Voltage-Gated Sodium Channel; C478638:Scn3a protein, rat
keywords: intrathecal delivery; lentivirions; neuropathic pain; spinal nerve ligation