Analgesic Effect Of Dexmedetomidine In Rats After Chronic Constriction Injury By Mediating Microrna-101 Expression And The E2f2-Tlr4-Nf-Kappa B Axis

New FindingsWhat is the central question of this study?Dexmedetomidine has a capacity for sedation, anti-anxiety and analgesia with minimal suppression of respiratory function; what is its role in neuropathic pain and what is the involvement of miRNAs? What is the main finding and its importance?Dexmedetomidine attenuates inflammation and apoptosis and the stimulation of TLR4-NF-kappa B signalling in rat spinal cord via miR-101 overexpression and E2F2 downregulation. The significant analgesic effect of dexmedetomidine (Dex) has been underscored in neuropathic pain (NPP), but the underlying mechanism remains unclear. This study explored the functional effect of Dex on microRNA (miR)-101-regulated E2 promoter binding factor 2 (E2F2) with the engagement of Toll-like receptor 4 (TLR4)-nuclear factor-kappa B (NF-kappa B) signalling. Chronic constriction injury (CCI) was performed to generate an NPP rat model. The expression of miR-101, E2F2 and TLR4-NF-kappa B signalling-relevant proteins was assessed by RT-quantitative PCR, immunoblotting and immunohistochemistry. Inflammatory factors were detected by enzyme-linked immunosorbent assay. The results showed that Dex increased mechanical withdrawal threshold and thermal latency to withdraw. The expression of interleukin (IL)-6, IL-8 and tumour necrosis factor-alpha was increased in CCI rats, but these trends were reversed by Dex. In addition, Dex repressed caspase-9 expression and apoptotic cell numbers in spinal cord tissues in CCI rats. Moreover, the expression of E2F2 was significantly increased, while miR-101 was diminished in CCI rats, which was reversed by Dex. Furthermore, miR-101 inhibitor, E2F2 restoration or administration of a TLR4-specific agonist weakened the effect of Dex. Together, these results suggest that Dex has the capacity to ameliorate NPP by regulating the miR-101-E2F2-TLR4-NF-kappa B axis in rats subjected to CCI.