Identification of lncRNA expression profile in the spinal cord of mice following spinal nerve ligation-induced neuropath

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RESEARCH

Identification of lncRNA expression profile in the spinal cord of mice following spinal nerve ligation‑induced neuropathic pain Bao‑Chun Jiang1,2†, Wen‑Xing Sun3†, Li‑Na He1,2, De‑Li Cao1,2, Zhi‑Jun Zhang1,2 and Yong‑Jing Gao1,2*

Abstract  Background:  Neuropathic pain that caused by lesion or dysfunction of the nervous system is associated with gene expression changes in the sensory pathway. Long noncoding RNAs (lncRNAs) have been reported to be able to regu‑ late gene expression. Identifying lncRNA expression patterns in the spinal cord under normal and neuropathic pain conditions is essential for understanding the genetic mechanisms behind the pathogenesis of neuropathic pain. Results:  Spinal nerve ligation (SNL) induced rapid and persistent pain hypersensitivity, characterized by mechanical allodynia and heat hyperalgesia. Meanwhile, astrocytes and microglia were dramatically activated in the ipsilateral spinal cord dorsal horn at 10 days after SNL. Further lncRNA microarray and mRNA microarray analysis showed that the expression profiles of lncRNA and mRNA between SNL and sham-operated mice were greatly changed at 10 days. The 511 differentially expressed (>2 fold) lncRNAs (366 up-regulated, 145 down-regulated) and 493 mRNAs (363 upregulated, 122 down-regulated) were finally identified. The expression patterns of several lncRNAs and mRNAs were further confirmed by qPCR. Functional analysis of differentially expressed (DE) mRNAs showed that the most signifi‑ cant enriched biological processes of up-regulated genes in SNL include immune response, defense response, and inflammation response, which are important pathogenic mechanisms underlying neuropathic pain. 35 DE lncRNAs have neighboring or overlapping DE mRNAs in genome, which is related to Toll-like receptor signaling, cytokine– cytokine receptor interaction, and peroxisome proliferator-activated receptor signaling pathway. Conclusion:  Our findings uncovered the expression pattern of lncRNAs and mRNAs in the mice spinal cord under neuropathic pain condition. These lncRNAs and mRNAs may represent new therapeutic targets for the treatment of neuropathic pain. Keywords:  LncRNA, Spinal cord, Spinal nerve ligation, Neuropathic pain Background Neuropathic pain is one of the most common chronic pain in humans and characterized by an increase in the responsiveness of nociceptive neurons in the peripheral *Correspondence: [email protected] † Bao-Chun Jiang and Wen-Xing Sun have contributed equally to this work 1 Pain Research Laboratory, Institute of Nautical Medicine, Jiangsu Key Laboratory of Inflammation and Molecular Drug Target, Nantong University, 9 Seyuan Road, Nantong 226019, Jiangsu, China Full list of author information is available at the end of the article

and central nervous system (CNS) [1]. Peripheral and central sensitization represents the altered functional status of nociceptive neurons and results from changes of a vast amount of functional protein and signaling pathways in the neuron and glial cell [2, 3]. Recent