LncRNA uc.48+ is involved in diabetic neuropathic pain mediated by the P2X3 receptor in the dorsal root ganglia

Abstract

Some long non-coding RNAs (lncRNAs) participate in physiological processes that maintain cellular and tissue homeostasis, and thus, the dysregulated expression of lncRNAs is involved in the onset and progression of many pathological conditions. Research has indicated that the genetic knockout of some lncRNAs in mice resulted in peri-or postnatal lethality or developmental defects. Diabetes mellitus (DM) is a major cause of peripheral neuropathy. Our studies showed that the expression levels of lncRNA uc.48+ in the diabetic rat dorsal root ganglia (DRG) and the DM patients' serum samples were increased. It suggested that lncRNA uc.48+ was involved in the pathophysiological process of DM. The aim of this study was to investigate the effects of lncRNA uc.48+ small interfering RNA (siRNA) on diabetic neuropathic pain (DNP) mediated by the P2X 3 receptor in the DRG. The values of the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured by the von Frey test and Hargreaves' test, respectively. The levels of P2X 3 protein and messenger RNA (mRNA) in the DRG were detected by reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, and western blotting. The experiments showed that the MWT and TWL values in DM rats were lower than those in the control rats. The MWT and TWL values in DM rats treated with lncRNA uc.48+ siRNA were increased compared to those in DM rats, but there was no significant difference between the DM rat group and the DM + scramble siRNA group. The levels of P2X 3 protein and mRNA in the DM DRG were higher than those in the control, while the levels of P2X 3 protein and mRNA in the DG of DM rats treated with uc.48+ siRNA were significantly decreased compared to those in DM rats. The expression levels of TNF-α in the DRG of DM rats treated with uc.48+ siRNA were significantly decreased compared to those in the DM group. The phosphorylation and activation of ERK1/2 in the DM DRG were decreased by uc.48+ siRNA treatment. Therefore, uc.48+ siRNA treatment may alleviate the DNP by inhibiting the excitatory transmission mediated by the P2X 3 receptor in DRG.

Nanoparticle-encapsulated emodin decreases diabetic neuropathic pain probably via a mechanism involving P2X3 receptor in the dorsal root ganglia

“…**p < 0.01 compared to the control group; ## p < 0.01 compared to the DM group and STZ-induced mechanical allodynia is mediated by P2X3 receptors in the DRG neurons [20]. DNP is a common complication of T2DM [3,26,[30][31][32]. Our results showed that thermal hyperalgesia and abnormal mechanical hyperalgesia in DM rats were increased compared with those in control rats.…”

The role of P2X3 receptors in bilateral masseter muscle allodynia in rats

“…It has been suggested that lip inflammation leads to increased P2X 3 receptors expression in TRG mediated by calcitonin gene-related peptide and could be involved in ectopic mechanical allodynia (31). In addition, some previous studies have determined enhanced P2X 3 receptors expression in dorsal root ganglion (DRG) after muscle inflammation (32). However, some studies claim that P2X 3 -expressing TRG neurons considerably differ from DRG afferent neurons, suggesting differences in pain transmission depending on the location of pain occurrence, and that the underlying mechanisms of pain originating from different body regions are unique (21,22).…”

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

“…It has been speculated that these ncRNAs are emerging key regulators of gene expression under physiological and pathological conditions (Wang and Chang, 2011; Yang et al, 2014; Li et al, 2016). Moreover, emerging data have shown that ncRNAs are of crucial importance in various types of pain, particularly NP (Chen et al, 2014; Shao et al, 2015; Zhang and Banerjee, 2015; Wang et al, 2016). However, the regulatory functions of ncRNAs in NP and their underlying functional mechanisms have not been systematically described.…”