Identification of IncRNA Expression Profile in the Spinal Cord of Mice following Spinal Nerve Ligation-Induced Neuropathic Pain

Abstract

BackgroundNeuropathic 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 regulate 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.ResultsSpinal 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 up-regulated, 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 significant 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.ConclusionOur 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.

Targeted disruption of the orphan receptor Gpr151 does not alter pain-related behaviour despite a strong induction in dorsal root ganglion expression in a model of neuropathic pain

“…The data described here shows that SNI induces a very clear difference in the mouse DRG 7 days after surgery between the marked 50-fold increase in Gpr151 mRNA and the modest, though significant, 20% decrease in the related receptors GalR1 and GalR2. These changes are comparable to previous reports: Reinhold described a 14.1 fold increase in Gpr151 in mouse DRG 7 days after the chronic constriction model of neuropathic pain (Reinhold et al, 2015) whilst Jiang described a 27.7 fold change in mouse DRG 10 days after the spared nerve ligation model of neuropathic pain (Jiang et al, 2015). The changes in DRG GalR1 and GalR2 mRNA expression are also comparable to previous reports following complete section of the sciatic nerve (axotomy), using in situ hybridization (Sten Shi et al, 1997, Xu et al, 1996) and quantitative RT-PCR (Hobson et al, 2006).…”

“…Several groups have used a range of techniques, which include transcriptional profiling and real-time quantitative RT-PCR, to identify and then quantify changes in gene expression in the rodent DRG and/or dorsal horn of the spinal cord after nerve injury models of neuropathic pain (Costigan et al, 2002, Griffin et al, 2003, Jiang et al, 2015, Reinhold et al, 2015). The data described here shows that SNI induces a very clear difference in the mouse DRG 7 days after surgery between the marked 50-fold increase in Gpr151 mRNA and the modest, though significant, 20% decrease in the related receptors GalR1 and GalR2.…”

“…The orphan G-protein coupled receptor (GPCR) Gpr151 is a member of the class A rhodopsin-like family and has recently been shown to be significantly up-regulated in the DRG following neuronal injury models of neuropathic pain (Jiang et al, 2015, Reinhold et al, 2015). Gpr151 was originally identified as having homology to galanin receptors, and variously designated as GPCR10, GPCR-2037, GalRL (Berthold et al, 2003, Ignatov et al, 2004, Takeda et al, 2002) or PGR7 (Vassilatis et al, 2003).…”

Identification of the Spinal Expression Profile of Non-coding RNAs Involved in Neuropathic Pain Following Spared Nerve Injury by Sequence Analysis

“…Recent studies have also shown that peripheral noxious stimuli induced changes in the expression of lncRNAs, which are associated with pain hypersensitivity underlying NP (Zhao et al, 2013). Previous research studies performed gene chip studies to screen and predict DE lncRNAs in the spinal cord SNL model mice (Jiang et al, 2015). Although much evidence has been found, no comprehensive analysis on ncRNAs involved in NP has been performed.…”

Effects of XIST/miR‐137 axis on neuropathic pain by targeting TNFAIP1 in a rat model

“…LncRNAs have served as important molecules which can regulate gene expression at transcriptional and post‐transcriptional levels (Knauss & Sun, ). It has been reported that identifying abnormal lncRNAs in the spinal cord under neuropathic pain conditions helps to understand the genetic mechanisms of neuropathic pain (Jiang, Sun, & He, ). For example, a kind of lncRNA can contribute to neuropathic pain by inhibiting Kcna2 in primary afferent neurons (Zhao, Tang, & Zhang, ).…”