miR-140 ameliorates neuropathic pain in CCI rats by targeting S1PR1

Abstract

Objectives

Neuropathic 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.

Methods

Rats 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.

Results

Decreased 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.

Conclusions

MiR-140 could mollify CCI-stimulated neuropathic pain via targeting S1PR1, suggesting a potential therapeutic target in the treatment of neuropathic pain.

Keywords:

• miR-140
• neuropathic pain
• neuroinflammation
• RASA1

Authors' contributions

JJL and YHW conceived and designed the experiments, YBZ and ZM analyzed and interpreted the results of the experiments, YL and ZPS performed the experiments

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

All data generated or analyzed during this study are included in this published article.