MiR-204-5p Alleviates Neuropathic Pain by Targeting BRD4 in a Rat Chronic Constrictive Injury Model.

Abstract

PurposeThe pathogenesis of neuropathic pain is complex, and previous studies have found that microRNAs are important regulators of neuropathic pain and are associated with the progression of neuropathic pain. This study aims to explore the level and role of miR-204-5p in the chronic constrictive injury (CCI) model of rats.Patients and MethodsThe CCI rat model was constructed to evaluate paw withdrawal threshold (PWT), paw withdrawal latency (PWL), the expressions of miR-204-5p, and the contents of inflammatory factors in the model. Overexpression of miR-204-5p in rat spinal cord was induced by intrathecal injection of miR-204-5p mimics. PWT and PWL were used to estimate mechanical and thermal pain thresholds. IL-6 and TNF-α were determined by ELISA. Luciferase reporter gene was conducted to verify the targeting relationship between miR-204-5p and BRD4.ResultsmiR-204-5p was abnormally down-regulated in the CCI group. The thresholds of mechanical and thermal pain stimulation in the CCI group were lower, and the levels of inflammatory factors were higher than those in the sham group. Overexpression of miR-204-5p alleviated PWT, PWL and inflammatory factors. Besides, the luciferase reporter gene showed that BRD4 was a target gene of miR-204-5p.ConclusionThese results suggested that miR-204-5p may alleviate neuropathic pain and inflammation through targeted regulation of BRD4 expression.