MicroRNA-106a-5p alleviates chronic constriction injury-induced neuropathic pain by targeting ten-eleven translocation 2 in a rat model.

Abstract

Objectives: Neuropathic pain (NP) is pain due to lesions or diseases of the somatosensory nervous system. microRNA-106a-5p (miR-106a-5p) is correlated with multiple illness processes. To probe the molecular mechanism of miR-106a-5p acting on NP.

Methods: The chronic constriction injury (CCI) rat model was applied to simulate NP in rats. RT-qPCR was utilized to detect miR-106a-5p and ten-eleven translocation methylcytosine dioxygenase 2 (TET2) levels. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) were used to validate the targeting relationship. Enzyme-linked immunosorbent assay (ELISA) was employed to monitor the inflammatory factors levels.

Results: The content of miR-106a-5p in the dorsal root ganglia (DRG) and spinal cord tissue of CCI rats was reduced by approximately 0.6-fold on postoperative day 21. Meanwhile, paw withdrawal threshold (PWT) and paw retraction latency (PWL) were reduced by approximately 0.4-fold. Notably elevated TNF-α, IL-1β and IL-6 while remarkably reduced IL-10 were discovered in CCI rats. Mechanistically, TET2 levels doubled in DGR and spinal cord tissues on postoperative day 21 and negatively regulated by miR-106a-5p. miR-106a-5p overexpression increased PWT and PWT of CCI rats, which can be reversed by upregulated TET2. Moreover, up-regulated miR-106a-5p suppressed TNF-α, IL-1β and IL-6 while increasing IL-10. This was partially reversed by TET2 overexpression.

Discussion: miR-106a-5p attenuates NP by negatively regulating TET2 to raise pain threshold as well as suppressing inflammatory responses in rats. By targeting miR-106a-5p, the lack of drug specificity in clinical settings will be solved.