The Mechanism Of Hyperalgesia And Anxiety Induced By Remifentanil: Phosphorylation Of GluR1 Receptor In Anter IOR Cingulate Cortex

Objective:During perioperative period administration with remifentanil may induce hyperalgesia?RIH?.Anterior Cingulate Cortex?ACC?is critical for pain,fear,and memory.Phosphorylation of the GluR1 receptor is important for ACC function.However,the mechanism of RIH development and in particular the potential interplay between ACC and Remifentanil induce hyperalgesia is yet to be elucidated.Methods:Local injection Ibotenic acid?IBO?or inhibitors of PKA?H89? r dimethyl sulfoxide?DMSO?to Anterior Cingulate Cortex,and followed by Remifentanil or saline intravenously infusion over 60 minutes in rats,Thereafter,the pain threshold were evaluated by the paw withdrawal echanical threshold?PWT?and paw withdrawal latency?PWL?.Anxiety behaviors were evaluated by open field test?OFT?and elevated plus maze?EPM?.Behaviors data were recorded at 0,2,6,24h after remifentanil nfusion.After behavior tests the expression of AMPA receptors subunits and their phosphorylation(Glu R1,GluR1^ser845)were analyzed by Western blotting,the expression of C-fos and Arc were analyzed by immunofluorescent staining.Result:In behavior tests,RIH and anxiety status were positively correlated,when the pain threshold was minimized anxiety behaviors were most ronounced.PKA inhibitor with H89 could attenuated RIH and anxiety.Western blotting showed when the pain threshold was minimized the xpression of phosphorylation GluR1^ser845increased significantly in ACC.And PKA inhibitor with H89 could attenuated expression of phosphorylation GluR1^ser845.Immunofluorescent staining showed when the pain threshold as minimized the expression of C-fos were highest and expression of Arc were lowest in ACC.And PKA inhibitor with H89 could decrease the xpression of C-fos and increased Arc in ACC.After ACC damaged remifentanil couldn't induced hyperalgesia and anxiety.Conclusion:The ACC is a critical hub for RIH and RIH related anxiety,and egulating phosphorylation of GluR1^ser845er845 may regulating RIH and anxiety.The interaction of hyperalgesia and anxiety in ACC is the mechanisms of individual differences characteristic of RIH.