Journal of Pain Research (Nov 2019)
Transcriptome Changes In Dorsal Spinal Cord Of Rats With Neuropathic Pain
Abstract
Song Cao,1,2 Jie Yuan,1,2 Dexing Zhang,1 Song Wen,1 Jie Wang,1 Ying Li,1 Wenwen Deng3 1Department of Pain Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, People’s Republic of China; 2Guizhou Key Laboratory of Anesthesia and Organ Protection, Zunyi Medical University, Zunyi 563003, People’s Republic of China; 3Department of Cardiology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, People’s Republic of ChinaCorrespondence: Ying LiDepartment of Pain Medicine, Affiliated Hospital of Zunyi Medical University, 149 Dalian Street, Zunyi 563000, People’s Republic of ChinaEmail [email protected] DengDepartment of Cardiology, Affiliated Hospital of Zunyi Medical University, 149 Dalian Street, Zunyi 563000, People’s Republic of ChinaEmail [email protected]: Mechanisms of neuropathic pain are not fully understood. Molecular changes in spinal dorsal horn take part in the initiation and development of neuropathic pain.Methods: To detect the transcriptome changes in the dorsal spinal cord of neuropathic pain rat, sciatic nerve chronic constriction injury (CCI) rats were used. Then, the CCI ipsilateral dorsal spinal cords of lumbar L3-L5 segments were collected at 14th day post-CCI and subjected to microRNA and long non-coding RNA (lncRNA)/mRNA microarray. To evaluate functions of differential mRNAs, bioinformatics methods including gene ontology (GO) and KEGG pathway analysis were conducted for significantly up- and downregulated mRNAs.Results: MicroRNA microarrays showed that 13 microRNAs were differently expressed between CCI and sham-operated rats (fold change ≥ 2.0). Six of them were upregulated, and the other seven were downregulated in CCI group. MicroRNA-1b overexpressed 18.7 times after CCI. LncRNA/mRNA microarray detected 876 lncRNAs with significant differential expression (fold change ≥ 2.0). Among them, 339 were significantly upregulated, and 537 were downregulated in CCI group. Sixteen of them differentially expressed more than 10 times and the lncRNA XR_356687 overexpressed as high as 53 times. In addition, 950 mRNAs were differentially expressed (fold change ≥ 2.0), including 405 upregulated and 545 downregulated in CCI group. Ten of these mRNAs with changed expressions of more than 10 times. The Hspa1b (encodes heat shock protein 70) overexpressed 24 times in CCI rats. Gene ontology analysis revealed that hundreds of differentially expressed mRNAs involved in the biological processes, cellular component, and molecular function. In addition, these genes significantly enriched into 32 KEGG pathways, including the TNF, FoxO, cytokine–cytokine receptor interaction, and calcium signaling pathways.Conclusion: Neuropathic pain induced comprehensive changes of transcription profile in the dorsal spinal cord. These differentially expressed transcripts in spinal cord could be potential targets in defeating neuropathic pain.Keywords: neuropathic pain, peripheral nerve injury, microRNA, long non-coding RNA, mRNA, pathways, spinal dorsal horn, chronic constriction injury
