Etomidate Relieves Oxaliplatin‐Induced Neuropathic Pain by Regulating AMPK/Nrf2/HO‐1 Axis

Etomidate (Eto) is extensively capitalized in clinical anesthesia induction. Whereas, the function of Eto in neuropathic pain caused by anticancer chemotherapeutic drug remains indistinct. Hereof, the research attempted to unveil the regulatory mechanisms of Eto in oxaliplatin (OXA) elicited neuropathic pain. The mice model was established by OXA induction and administrated by Eto along with the concentrations of 1.5, 3, and 6 mg/kg. The neuropainful behaviors such as paw withdrawal threshold (PWT), flinches, paw withdrawal latency (PWL) and latency were analyzed. The influences of Eto on inflammatory response and oxidative stress in OXA model were explored by HE staining, RT-qPCR, western blot and the corresponding kits. AMPK/Nrf2/HO-1 pathways were studied to uncover the potential mechanism. After creation of C6 cells model, the effects of Eto in neuropathic pain were further investigated in vitro. Eto significantly relieved OXA-irritated neuropainful behaviors via elevating the values of PWT and PWL, declining the number of spontaneous flinches, meanwhile restoring latency to fall. Moreover, Eto triggered a robust anti-inflammatory response, which lowered inflammatory scores and suppressed GFAP, IL-1β, TNF-α and NLRP3 expression. Additionally, Eto obviously enhanced SOD and GSH levels, but reduced MDA and COX2 levels, thereby mitigating OXA-induced oxidative stress response. Mechanism study discovered that activation of AMPK/Nrf2/HO-1 pathways participated in regulating the neuroprotective function of Eto in inflammatory response and oxidative stress response in OXA-treated mice and in C6 cells model. In conclusions, Eto improved OXA-induced neuropathic pain by regulating AMPK/Nrf2/HO-1 pathway.