Identification Of LncRNAs In The Paraventricular Nucleus Of A Lumbar Disc Herniation Rat Model

Background:Radicular pain,which can be caused by a lesion or autologous nucleus pulposus(NP)implantation,is associated with gene expression changes in the pain signalling pathway.Long noncoding RNAs(lncRNAs)and Messenger RNAs(mRNAs)have been recently shown to play critical roles in neuropathic pain.However,little is known about the mechanistic role of lncRNAs in lumbar disc herniation(LDH).Identifying lncRNAs and mRNAs expression patterns in the nuclei paraventricularis under normal and NP-implantation conditions is essential for understanding the genetic mechanisms of neuropathic pain..The results:Lumbar disc herniation(LDH)induced rapid and persistent pain hypersensitivity,which was characterized by mechanical allodynia and heat hyperalgesia.Meanwhile,the lncRNA microarray and mRNA microarray analyses showed that the expression profiles of lncRNAs and mRNAs between the LDH and sham groups were markedly changed at 7 days post operation.A total of 322differentially expressed(>1.5-fold)lncRNAs(124 up-regulated,198down-regulated)and 166 mRNAs(77up-regulated,89 down-regulated)were identified.The expression patterns of several lncRNAs and mRNAs were further confirmed by qPCR.Functional analysis of the differentially expressed mRNAs showed that the most significant enriched biological processes of the up-regulated genes in LDH included celluar responde to peptide hormone stimulus,mitocgondrial large ribosomal subunit,transcription coactivator activity and Neuroactive ligand-receptor interaction.which are important pathogenic mechanisms underlying neuropathic pain.Using high-throughput sequencing technique,we found that P2X2 and Kcnip3 genes expression in the paraventricular nucleus of LDH rats increased significantly,while Avp and BDNF genes expression decreased significantly.Conclusion:Our findings revealed the expression pattern of lncRNAs and mRNAs in the rat spinal cord under neuropathic pain conditions.These lncRNAs and mRNAs may represent new therapeutic targets for the treatment of radicular pain.Using high-throughput sequencing technique,we found that P2X2 and Kcnip3 genes expression in the paraventricular nucleus of LDH rats increased significantly,while Avp and BDNF genes expression decreased significantly.This result suggests that P2X2,Kcnip3,Avp and BDNF in the nuclei paraventricularis may be involved in the pain sensitization of LDH,which needs further researches.