Effect of etomidate on spinal microglia activation in rats with chronic neuropathic pain and its mechanism

Objective: To explore the effect of etomidate (Eto) on the activation of spinal microglia in chronic neuropathic pain (NP) rats by regulating CXC chemokine ligand 12 (CXCL12)/CXC chemokine receptor 4 (CXCR4) signal pathway.Methods: A total of 36 SD rats were randomly divided into 6 groups (6 rats/group): Sham group, Model group, positive control group (150 mg/kg sodium ferulate), Eto low dose group (0.3 mg/kg), Eto medium dose group(0.9 mg/kg), and Eto high dose group(2.7 mg/kg).Except for the Sham group, the NP model of rats was established by chronic compression injury of sciatic nerve (CCI).After successful modeling, Eto was injected through tail vein or sodium ferulate was administered by gavage once a day for 4 weeks.Mechanical foot contraction reflex threshold (MWT) and thermal stimulation foot contraction reflex latency (TWL) were measured 2 hours before operation and 3, 5, 7 and 10 days after operation respectively; immunohistochemical staining was performed on L4-L6 spinal cords to observe the expression of ionic calcium junction protein 1 (Iba-1) protein in microglia; the expression of Iba-1 mRNA was detected by real-time fluorescent quantitative polymerase chain reaction (RT-qPCR); the contents of tumor necrosis factor(TNF)-α, interleukin(IL)-6 and IL-1β in the spinal cord were detected by enzyme-linked immunosorbent assay(ELISA); western blotting was used to detect the expressions of CXCL12, CXCR4 and Iba-1 proteins in the spinal cord.Results: Compared with Sham group, the MWT and TWL in rats of Model group were obviously reduced, while the IOD value of Iba-1 expression and Iba-1 mRNA expression, contents of TNFα, IL-6, IL-1β, expressions of CXCL12, CXCR4, Iba-1 protein increased (P＜0.05); compared with the Model group, the MWT and TWL in rats of Eto low, medium and high dose groups obviously increased, the IOD value of Iba-1 expression, Iba-1 mRNA expression, contents of TNF-α, IL-6 and IL-1β and expressions of CXCL12, CXCR4, Iba-1 protein decreased (P＜0.05), and there was no obvious difference between Eto high dose group and positive control group in the above indicators(P＞ 0.05).Conclusion: Eto may play a role in relieving NP by inhibiting CXCL12/CXCR4 signal pathway, inhibiting inflammatory reaction and activation of spinal microglia.