Referenced in: none

Automatically associated channels: Nav1.3

Title: Intrathecal miR-183 delivery suppresses mechanical allodynia in mononeuropathic rats.

Authors: Chung-Ren Lin, Kuan-Hung Chen, Chien-Hui Yang, Hui-Wen Huang, Shyr-Ming Sheen-Chen

Journal, date & volume: Eur. J. Neurosci., 2014 May , 39, 1682-9

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24612023

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.