LncRNA X inactive specific transcript contributes to neuropathic pain development by sponging miR‐154‐5p via inducing toll‐like receptor 5 in CCI rat models

Noncoding RNAs, including long non‐coding RNAs (lncRNAs) and microRNAs, are involved in the development of neuropathic pain. Currently, we investigated that lncRNA X inactive–specific transcript (XIST) and toll‐like receptor 5 (TLR5) were greatly upregulated in chronic constriction injury rat models, whereas miR‐154‐5p (microRNA‐154‐5p) was significantly downregulated. Bioinformatics analysis was used to predict miR‐154‐5p as a target gene of XIST, and dual‐luciferase reporter tests proved the correlation between them. We observed that miR‐154‐5p was negatively modulated by XIST in vitro. XIST overexpression markedly induced neuropathic pain development in rats with chronic constriction injury, whereas the upregulation of miR‐154‐5p could reverse this phenomenon. Furthermore, TLR5 was demonstrated to be a target gene of miR‐154‐5p by using bioinformatics predictions. miR‐154‐5p negatively regulated TLR5 expression in vitro, and TLR5 was able to promote neuropathic pain development. In addition, overexpressing miR‐154‐5p can reverse the role of TLR5 neuropathic pain in vivo. Taken these together, we indicated that XIST could increase TLR5 expression by acting as a sponge of miR‐154‐5p in neuropathic pain development. This study revealed that XIST can contribute to neuropathic pain progression in rats through decreasing miR‐154‐5p and increasing TLR5. The XIST/miR‐154‐5p/ TLR5 axis can be provided as a novel therapeutic target in treating neuropathic pain. We showed that the inhibition of X inactive–specific transcript (XIST) inhibited neuropathic pain development of chronic constriction injury rats via increasing miR‐154 and decreasing toll‐like receptor 5 (TLR5). Both in vitro and in vivo experiments were performed to elucidate the mechanisms of the XIST/miR‐154/TLR5 axis in modulating neuropathic pain development. Our findings implied that XIST can be identified as a novel therapeutic target for neuropathic pain.