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.