MiR-30b Attenuates Neuropathic Pain by Regulating Voltage-Gated Sodium Channel Nav1.3 in Rats.

Songxue Su,Xiuhua Ren,Weidong Zang,Bo Xu,Xuemei Chen,Jinping Shao,Jing Cao,Lei Li,Qingzan Zhao,Jian Wang,Weihua Cai,Qian Bai

doi:10.3389/fnmol.2017.00126

Abstract

Nav1.3 is a tetrodotoxin-sensitive isoform among voltage-gated sodium channels that are closely associated with neuropathic pain. It can be up-regulated following nerve injury, but its biological function remains uncertain. MicroRNAs (miRNAs) are endogenous non-coding RNAs that can regulate post-transcriptional gene expression by binding with their target mRNAs. Using Target Scan software, we discovered that SCN3A is the major target of miR-30b, and we then determined whether miR-30b regulated the expression of Nav1.3 by transfecting miR-30b agomir through the stimulation of TNF-α or by transfecting miR-30b antagomir in primary dorsal root ganglion (DRG) neurons. The spinal nerve ligation (SNL) model was used to determine the contribution of miR-30b to neuropathic pain, to evaluate changes in Nav1.3 mRNA and protein expression, and to understand the sensitivity of rats to mechanical and thermal stimuli. Our results showed that miR-30b agomir transfection down-regulated Nav1.3 mRNA stimulated with TNF-α in primary DRG neurons. Moreover, miR-30b overexpression significantly attenuated neuropathic pain induced by SNL, with decreases in the expression of Nav1.3 mRNA and protein both in DRG neurons and spinal cord. Activation of Nav1.3 caused by miR-30b antagomir was identified. These data suggest that miR-30b is involved in the development of neuropathic pain, probably by regulating the expression of Nav1.3, and might be a novel therapeutic target for neuropathic pain.Perspective: This study is the first to explore the important role of miR-30b and Nav1.3 in spinal nerve ligation-induced neuropathic pain, and our evidence may provide new insight for improving therapeutic approaches to pain.

Highlights

The IASP (International Association for the Study of Pain) defines pain as an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage (Merskey, 1979)
We focused on miR-30b, and we intended to verify whether miR-30b could regulate the expression of Nav1.3, as well as to explore the possibility that miR-30b could potentially alleviate neuropathic pain by changing the expression of Nav1.3 in dorsal root ganglion (DRG) and the spinal cord
We discovered that SCN3A was the primary target of miR-30b using Target Scan software

Summary

Introduction

The IASP (International Association for the Study of Pain) defines pain as an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage (Merskey, 1979). Nav1.3 is a subunit among the VGSCs, encoded by the SCN3A gene, and located on chromosome 2 (Estacion et al, 2010). Epilepsy (Guo et al, 2008; Vanoye et al, 2014), mental retardation (Bartnik et al, 2011), autism (Celle et al, 2013), and neuropathic pain (Chen et al, 2014) are perhaps caused by the aberrant expression of SCN3A. The mechanism of altered Nav1.3 expression continues to perplex. It was reported that inhibition of the expression of NF-K B could prevent neuropathic pain by suppressing Nav1.3 re-expression in an L5-VRT model (Hains et al, 2004). Several studies focused on intrathecal lidocaine delivery to attenuate neuropathic pain through modulating Nav1.3 expression and reducing the activation of the spinal microglial (Zang et al, 2010)

Results

Discussion

Conclusion