Premium
Intrathecal miR‐183 delivery suppresses mechanical allodynia in mononeuropathic rats
Author(s) -
Lin ChungRen,
Chen KuanHung,
Yang ChienHui,
Huang HuiWen,
SheenChen ShyrMing
Publication year - 2014
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.12522
Subject(s) - neuropathic pain , downregulation and upregulation , allodynia , dorsal root ganglion , medicine , intrathecal , anesthesia , nerve injury , neurotrophic factors , real time polymerase chain reaction , hyperalgesia , nociception , endocrinology , chemistry , dorsum , anatomy , receptor , gene , biochemistry
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.