Comparative Transcriptome Profiling Reveals Changes of microRNAs Response to Exercise in Rats with Neuropathic Pain.

Jia-Bao Guo,Qing Cao,Bing-Lin Chen,Xue-Qiang Wang,Ying Wang,Yi Zhu,Yi-Li Zheng,Ge Song,Zheng Yang,Xuan Su,Pei-Jie Chen,Laura Baroncelli

doi:10.1155/2021/5597139

Abstract

There is accumulating evidence showing that exercise therapy may play an active role in peripheral neuropathic pain (NP), but its mechanism is still unclear. Studies have found that microRNAs (miRNAs) may play a role in NP by regulating pain-related target genes. Therefore, we aimed to explore the changes of miRNA and mRNA of dorsal root ganglion (DRG) after NP in response to exercise with transcriptome technology. The chronic constriction injury (CCI) model was established, and rats were randomly allocated into three groups, namely, the sham-operated, CCI, and CCI-exercised groups. L4-L6 DRG tissue was taken for RNA-sequencing, and the differentially expressed genes (DEGs) were determined through bioinformatics analysis. Real-time PCR was used to confirm the accuracy. A total of 4 overlapping differentially expressed miRNAs and 186 overlapping differentially expressed mRNAs were identified in the two comparisons of the sham-operated group versus the CCI group and the CCI group versus the CCI-exercised group. Among these DEGs, miR-145-5p, miR-341, miR-300-5p, miR-653-5p, Atf3, Cacna2d1, Gal, and Ctss related to NP were validated by real-time PCR. DEGs between the CCI and CCI-exercised groups were enriched in HIF-1 signaling pathway, Rap1 signaling pathway, and neurotrophin signaling pathway. This study provides an understanding of the adaptive mechanisms after exercise of NP, and these DEGs in DRG might play a role in NP by stimulating the enriched pathways.

Highlights

Neuropathic pain (NP) is an unpleasant sensory and emotional experience caused by a lesion of or disease to the somatosensory system [1]
The constriction injury (CCI) and CCI-exercised groups showed no significant difference in body weight when compared with the sham group (Figure 3(a))
Results demonstrated that the Mechanical Withdrawal Threshold (MWT) of the CCI and CCI-exercised groups were significantly lower than that of the sham-operated group on the 3rd (p < 0:01), 7th (p < 0:01), and 14th (p < 0:01) postoperative days (Figure 3(b))

Summary

Introduction

Neuropathic pain (NP) is an unpleasant sensory and emotional experience caused by a lesion of or disease to the somatosensory system [1]. NP has poor response to standard analgesics; only 33%–50% patients benefit from first-line analgesics [2]. Some evidence that exercise can be safe and beneficial for pain management for NP has been observed in a population of peripheral NP patients [4,5,6,7]. Aerobic exercise can increase motor conduction velocity and epidermal innervation and decrease pain ratings in people with diabetic peripheral neuropathy [8, 9]. The mechanism of exercise training in improving NP induced by peripheral nerve injury has been discussed in some preclinical rodent studies, such as by decreasing proinflammatory cytokine expression [10,11,12], the molecular mechanisms triggering and maintaining these benefits remain poorly understood

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