Transcriptome Analysis of Non-coding RNAs and mRNAs in the Dorsal Root Ganglion of Peripheral Nerve Injury-Induced Neuropathic Pain.

Abstract

Maladaptive changes in gene expression at transcriptional level in dorsal root ganglia (DRGs) after nerve injury are critical for neuropathic pain genesis. Emerging evidence reveals the important role of non-coding RNAs (ncRNAs) in regulating gene transcription. Recent studies also have showed the contribution of ncRNAs to neuropathic pain. However, the expression profile of ncRNAs in the DRGs and potential regulatory mechanism in peripheral nerve injury-induced neuropathic pain are not fully clear. We used bCCI neuropathic pain model induced by chronic constriction injury of bilateral sciatic nerves to study the expression profile and potential functional mechanism of micro RNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs) and messenger RNA (mRNA) in the DRGs by RNA sequencing and bioinformatics analysis. A total of 47 miRNAs, 337 lncRNAs, 32 circRNAs, and 2269 mRNAs were differentially expressed (DE) in the DRGs of CCI mice 14 days after surgery. KEGG analysis demonstrated nociception-related signaling pathways were significantly enriched for DEncRNAs, including Rap1, Ras, and Hippo signaling pathway. GO analysis showed neuron related biological process, membrane related cell components, and binding related molecular functions were significantly enriched. The competing endogenous RNA (ceRNA) regulatory network of DEmiRNA-DEmRNA, DElncRNA-DEmRNA, and DEcircRNA-DEmiRNA existed in the DRGs of mice with neuropathic pain induced by peripheral nerve injury. In addition, 81 pain-related DE genes had protein-protein interactions (PPI) with each other. Our findings indicated that ncRNAs are involved in the development of peripheral nerve injury-induced neuropathic pain. DEncRNAs may provide us with a new perspective in chronic neuropathic pain research and may become a potential target for pain treatment.