• Jiajia Li, Yunbo Zhu, Zheng Ma, Yi Liu, Zhipeng Sun, and Yinghui Wu.
• Department of Neurology, Affiliated Hospital of Chengde Medical University, Chengde City, Hebei Province, China.
• J. Recept. Signal Transduct. Res. 2021 Aug 1; 41 (4): 401-407.

ObjectivesNeuropathic pain, with lots of clinical conditions in various diseases, whose physiopathology is implicated in inflammation. MicroRNAs (miRNAs) have largely been shown to exert anti-inflammatory effects against chronic diseases. We then evaluated the effects and regulatory mechanism of miR-140 on neuropathic pain.MethodsRats model with neuropathic pain were established via chronic constriction injury (CCI) and verified by determination of mechanical withdrawal threshold (MWT) and paw withdrawal latency (PWL). The expression level of miR-140 was determined via qRT-PCR (quantitative real-time polymerase chain reaction). Intrathecal injection of miR-140 agomiR was conducted to evaluate the influence of miR-140 on CCI rats via evaluation of MWT, PWL and inflammatory factors secretion. The binding target of miR-140 was predicted and characterized via dual luciferase activity assay.ResultsDecreased MWT and PWL, as well as increased inflammatory factor secretion, including IL (interleukin)-1β, IL-6 and interferon-γ (IFN-γ), were found in rats under CCI compared with sham rats. MiR-140 was decreased in rats under CCI. Intrathecal injection of miR-140 agomiR increased MWT and PWL, thus attenuating mechanical and thermal hyperalgesia in CCI rats. Moreover, decreased inflammatory factor secretion in rats under CCI injected with miR-140 agomiR, suggesting a negatively regulatory role of miR-140 on neuroinflammation. MiR-140 could bind with Sphingosine-1-phosphate receptor 1 (S1PR1). S1PR1 agonist, SEW2871, could reverse the suppression of miR-140 on neuropathic pain.ConclusionsMiR-140 could mollify CCI-stimulated neuropathic pain via targeting S1PR1, suggesting a potential therapeutic target in the treatment of neuropathic pain.

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