LncRNA?027537.2 Rge ? Lates P2X2 Receptor To Increases Central Pain Sensitivity In A Rat Lumbar Disc Herniation Model

Purpose:Lumbar disc herniation(LDH),one of the common causes of chronic pain,can induce central nervous hypersensitivity or Neuropathic pain(NP)and its incidence trends to raise year by year in the world,which has become a very serious problem.It is urgent to develop new molecuLar targets to treat LDH-induced pain due to the phenomenon in which little conventional drugs can be achieved complete analgesic effect.lncRNAs and mRNAs expression patterns in the paraventricuLar nuclei(PVN)under normal and NP-implantation conditions have been identified in previous research.Our research was designed to determine the role and genetic mechanisms of lncRNA?027537.2 in a NP rat model induced by LDH.Methods:1.The chronic pain model of Lumbar disc herniation(LDH)group and sham operation(sham)group were established from SD male rats after 3-8 weeks of ad ? Lt development.Persistent pain hypersensitivity were assessed by Paw withdrawal thresholds(PWT)and thermal paw withdrawal latencies(PWL)which had been accepted as a efficient way internationally.2.The RT-PCR was designed to detected the differently RNA expression levels of P2X2 and lncRNA?027537.2 in rats'PVN on 3d,7d,14d,21d after surgery.The protein expression of P2X2 in Several significant cerebral nucleis were detected by Western Blot between LDH and sham groups.3.Targeted injection of P2X2-siRNA and lncRNA?027537.2-siRNA in PVN region was used to measure the central pain hypersensitivity of LDH rats.4.The co-expression and distribution of P2X2 protein was checked by immunohistochemistry(IHC)in brain neurocyte.c-Fos positive nerve cells rate was determined to quantitatively analyse pain hypersensitivity in LDH rats.Res ? Lts:1.PWT and PWL of rat behavior significantly differently performanced from LDH and Sham group which began at 3days,peaked at 7days and returned to normal level at 35 days after LDH.2.LDH significantly upg ? Lated the expression of lncRNA?027537.2 and P2X2 receptor while had little influence on P2x1,3,4,7 receptors,and the nubmer of c-Fos positive neurons also increased in PVN region from LDH rats.3.IHC showed P2X2 was mainly distributed in NueN-positive neurons in PVN region of LDH rats,and had no co-expression with astroglia and microglial cells marked by GFAP and CD11b.4.Targeted injection of LncRNA?027537.2-siRNA and P2X2-siRNA significantly downreg ? Lated PWT of LDH rats and relieved central pain sensitization by the molec ? Lar mechanism of PVN region involved in.5.1ncRNA?027537.2 administration also significantly downreg ? Lated c-Fos and P2X2 positive nerve cells in PVN region,which suggested LncRNA?027537.2,as an upstream molec ? Le,reg ? Lates P2X2 receptors and mediates central pain sensitivity.Conclusion:lncRNA?027537.2 participates in central pain hyperreactivity in paraventric ? Laris nuclei of LDH rats by upreg ? Lating the expression of P2X2.This study revealed the mechanism of neuropathic pain in LDH,to some extent,might provided insight for a new treatment of LDH-induced pain by targeted molecuLar.