Changes in the expression of IL-6-Mediated MicroRNAs in the dorsal root ganglion under neuropathic pain in mice

• Published in: Synapse (New York, N.Y.) N.Y.), 2016-08, Vol.70 (8), p.317-324
• Main Authors: Hori, Naosuke, Narita, Michiko, Yamashita, Akira, Horiuchi, Hiroshi, Hamada, Yusuke, Kondo, Takashige, Watanabe, Moe, Igarashi, Katsuhide, Kawata, Miho, Shibasaki, Masahiro, Yamazaki, Mitsuaki, Kuzumaki, Naoko, Inada, Eiichi, Ochiya, Takahiro, Iseki, Masako, Mori, Tomohisa, Narita, Minoru
• Format: Article
• Language: English
• Subjects: Animals; DRG; exosome; Exosomes - metabolism; Ganglia, Spinal - metabolism; Interleukin-6 - metabolism; Male; Mice; Mice, Inbred C57BL; microRNA; MicroRNAs - genetics; MicroRNAs - metabolism; Neuralgia - genetics; Neuralgia - metabolism; neuropathic pain; Sensory Receptor Cells - metabolism
• ISSN: 0887-4476; 1098-2396
• DOI: 10.1002/syn.21902

A multiplex analysis for profiling the expression of candidate microRNAs (miRNAs), which are small noncoding RNAs that function as key post‐transcriptional regulators, may lead to a better understanding of the complex machinery of neuropathic pain. In the present study, we performed a miRNA array analysis using tissues of the dorsal root ganglion (DRG), a primary site for pain processing, obtained from mice with partial sciatic nerve ligation. Among 1135 total miRNAs, 26 miRNAs showed up‐regulation (more than 2‐fold change) and only 4 miRNAs showed down‐regulation (less than 0.5‐fold change) in the DRG of nerve‐ligated mice. In a RT‐qPCR assay, the levels of miR‐21, miR‐431, and miR‐511‐3p were significantly increased on the ipsilateral side of the DRG from 3 to 7 days after sciatic nerve ligation. These elevations were almost absent in IL‐6 knockout mice. Furthermore, the expression level of miR‐21, but not those of miR‐431 or miR511‐3p, was significantly increased in exosomes extracted from blood of nerve‐ligated mice. These findings suggest that the increased expression of IL‐6‐regulated miR‐21, miR‐431, and miR‐511‐3p in the DRG and increased exosomal miR‐21 extracted from blood after sciatic nerve ligation may play at least a partial role in neuropathic pain. Synapse 70:317–324, 2016. © 2016 Wiley Periodicals, Inc. Sciatic nerve ligation induces the increase in the expression of miR‐21 in the DRG and blood exosomes via IL‐6 signaling pathway. Therefore, miR‐21 could be a diagnostic biomarker for the neuropathic pain.