Inhibition of MicroRNA-15a/16 Expression Alleviates Neuropathic Pain Development through Upregulation of G Protein-Coupled Receptor Kinase 2
10.4062/biomolther.2018.073
- Author:
Tao LI
1
;
Yingchun WAN
;
Lijuan SUN
;
Shoujun TAO
;
Peng CHEN
;
Caihua LIU
;
Ke WANG
;
Changyu ZHOU
;
Guoqing ZHAO
Author Information
1. Department of Anesthesiology, China-Japan Union Hospital, Jilin University, Jilin 130033, China. zhaoguoqing_cjuh@163.com
- Publication Type:Original Article
- Keywords:
GRK2;
miR-15a/16;
Neuropathic pain;
p38 MAPK
- MeSH:
Animals;
Computational Biology;
Constriction;
Down-Regulation;
Hyperalgesia;
Inflammation;
Injections, Spinal;
Mice;
MicroRNAs;
Neuralgia;
p38 Mitogen-Activated Protein Kinases;
Phosphotransferases;
Protein Kinases;
Rats;
Sciatic Nerve;
Spinal Cord;
Up-Regulation
- From:Biomolecules & Therapeutics
2019;27(4):414-422
- CountryRepublic of Korea
- Language:English
-
Abstract:
There is accumulating evidence that microRNAs are emerging as pivotal regulators in the development and progression of neuropathic pain. MicroRNA-15a/16 (miR-15a/16) have been reported to play an important role in various diseases and inflammation response processes. However, whether miR-15a/16 participates in the regulation of neuroinflammation and neuropathic pain development remains unknown. In this study, we established a mouse model of neuropathic pain by chronic constriction injury (CCI) of the sciatic nerves. Our results showed that both miR-15a and miR-16 expression was significantly upregulated in the spinal cord of CCI rats. Downregulation of the expression of miR-15a and miR-16 by intrathecal injection of a specific inhibitor significantly attenuated the mechanical allodynia and thermal hyperalgesia of CCI rats. Furthermore, inhibition of miR-15a and miR-16 downregulated the expression of interleukin-1β and tumor-necrosis factor-α in the spinal cord of CCI rats. Bioinformatic analysis predicted that G protein-coupled receptor kinase 2 (GRK2), an important regulator in neuropathic pain and inflammation, was a potential target gene of miR-15a and miR-16. Inhibition of miR-15a and miR-16 markedly increased the expression of GRK2 while downregulating the activation of p38 mitogen-activated protein kinase and NF-κB in CCI rats. Notably, the silencing of GRK2 significantly reversed the inhibitory effects of miR-15a/16 inhibition in neuropathic pain. In conclusion, our results suggest that inhibition of miR-15a/16 expression alleviates neuropathic pain development by targeting GRK2. These findings provide novel insights into the molecular pathogenesis of neuropathic pain and suggest potential therapeutic targets for preventing neuropathic pain development.
