Dexmedetomidine alleviates microglial activation of neuropathic pain by modulating miR-23a/PDE10A axis in streptozotocin-induced diabetic mice

Abstract

Purpose: To elaborate the functional role of dexmedetomidine (DEX) in alleviating microglial activation of diabetic neuropathic pain (DNP) and explore the involved signaling pathways. Methods: The viability of BV-2 cells was measured using a commercial kit. Levels of interleukin 1β (IL- 1β) and tumor necrosis factor-α (TNF-α) were measured using commercial ELISA kit. The mRNA target was predicted and confirmed using TargetScan and luciferase assay. Protein expression levels were determined by western blotting. Diabetes was indiced in C57BL/6J mice using streptozotocin (STZ) and antidiabetic parameters evaluated in vivo. Results: DEX suppressed HG-induced microglial activation in BV-2 cells. The levels of IL-1β and TNF-α increased in HG-treated cells, but this was counteracted following DEX treatment. Phosphorylation of p65 (p-p65) was upregulated in cells treated with HG, while DEX repressed this upregulation. MiR-23a was downregulated in BV-2 cells treated with HG, but upregulated by addition of DEX. MiR-23a mimics repressed the induction of IL-1β and TNF-α levels and expression of p-p65. Results from TargetScan and luciferase assays showed that the 3-untranslated region (UTR) of PDE10A was directly targeted by miR-23a. The in vivo studies showed that miR-23a agomir relieved neuropathic pain and reduced the expressions of PDE10A and p-p65 in STZ-induced diabetic mice, but these effects were aggravated by DEX. Conclusion: The results show that upregulation of miR-23a, DEX alleviates microglial activation of neuropathic pain and reduces levels of inflammatory factors in STZ-induced diabetic C57BL/6J mice. The underlying mechanism was at least partially mediated by PDE10A.