title: Downregulation of microRNA-218 relieves neuropathic pain by regulating suppressor of cytokine signaling 3.
abstract: Neuropathic pain is an incapacitating disease that affects a large number of people worldwide, but effective therapies have not yet been established. microRNAs (miRs) are short non-coding RNAs that participate in several biological processes and states, including neuropathic pain. Nevertheless, the precise role of miRs in regulating neuropathic pain remains largely unknown. In the present study, we investigated the role of miR-218 in neuropathic pain using a rat model of chronic constriction injury (CCI). miR-218 expression was induced and studied in the spinal cord and microglial cells of rats with CCI. We noted that downregulation of miR-218 by a specific miR-218 inhibitor significantly attenuated mechanical allodynia, thermal hyperalgesia, and proinflammatory cytokine release in CCI rats. A dual-luciferase reporter assay, RT-qPCR, and western blot analysis results demonstrated that miR-218 directly targeted the 3'-UTR of the suppressor of cytokine signaling 3 (SOCS3) and regulated mRNA and protein expression of SOCS3. Treatment with miR-218 inhibitors inactivated Janus kinase/signal transducer and activator of transcription 3 (STAT3) signaling in rats with CCI in vivo. Moreover, miR-218 inhibitors significantly inhibited the activation of microglial cell STAT3 signaling and downstream proinflammatory genes in microglial cells. These results suggest that miR-218 regulated neuropathic pain and neuroinflammation by regulating SOCS3 expression, which negatively mediated STAT3 signaling. Thus, we propose that silencing of miR-218 may be a promising and novel treatment for neuropathic pain.
authors.affiliation: Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.
authors.forename: Longyun
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Zhao
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D015536:Down-Regulation; D005260:Female; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009437:Neuralgia / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000071223:Suppressor of Cytokine Signaling 3 Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: C547684:MIRN218 microRNA, mouse; D035683:MicroRNAs; D000071223:Suppressor of Cytokine Signaling 3 Protein