Abstract
MicroRNAs (miRNAs) play crucial roles in the pathogenesis of neuropathic pain. The present study investigated the effects of miR-448 on the progression of neuropathic pain in a rat model of chronic constriction injury (CCI) of the sciatic nerve. Reverse-transcription quantitative polymerase chain reaction was conducted to detect the gene expression. The paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were used to assess the pain threshold. The protein expression levels of interleukin (IL)-6, IL-1β and tumor necrosis factor-α (TNF-α) were detected by ELISA. The target of miR-448 was predicted by TargetScan software. The Student's t-test or one-way ANOVA were used to identify statistical differences among groups. miR-448 was persistently upregulated in CCI rats, and both mechanical allodynia and thermal hyperalgesia in CCI rats were decreased following miR-448 downregulation. The expression levels of IL-1β, IL-6 and TNF-α were significantly increased in CCI rats compared with controls, and these effects were reversed following treatment with a miR-448 inhibitor. A luciferase reporter assay revealed that sirtuin 1 (SIRT1) was a target gene of miR-448. SIRT1 was found to abrogate the effect of miR-448 on neuropathic pain development. Collectively, the results of the present study revealed that miR-448 promoted neuropathic pain in CCI rats by regulating neuroinflammation via SIRT1. Therefore, SIRT1 may be considered as a novel biomarker for neuropathic pain.