期刊
EUROPEAN JOURNAL OF NEUROSCIENCE
卷 39, 期 10, 页码 1682-1689出版社
WILEY-BLACKWELL
DOI: 10.1111/ejn.12522
关键词
lentivirions; neuropathic pain; spinal nerve ligation; intrathecal delivery
资金
- Chang Gung Memorial Hospital Research, Kaohsiung, Taiwan [880891, 880892, 880893, 891251, 8A1011]
- Taiwan National Science Council Research, Taipei, Taiwan [96-2628-B-182A-005-MY3, 98-2314-B-182A-035-MY2, 100-2314-B-182A-037, 101-2314-B-182A-014, 101-2314-B-182A-068-MY3]
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) 2weeks 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.
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