Analgesic effect of intra-amygdala infusion of U0126 on fentanyl-induced hyperalgesia in rats / 临床麻醉学杂志

ABSTRACT

Objective To explore the role of extracellular signal-regulated kinase (ERK)in central nucleus of amygdala (CeA)in the mechanism of fentanyl-induced hyperalgesia (OIH)in rats. Methods Step 112 healthy male Sprague-Dawley rats,weighing 60-100 g,were randomly divided into OIH and Control group.The mechanical paw withdrawal threshold (PWT)and the thermal paw withdrawal latency (PWL)were tested at pre-and post-OIH induction.Then the level of p-ERK in the CeA was analyzed by Western blotting.Step 2After successful induction of OIH and catheterization in CeA,another 30 SD male rats were randomly divided into 5 groups (n = 6 each)Group OIH;Group OIH+U0124;Group OIH+U0126(0.1 5 nmol);Group OIH+U0126(0.45 nmol)and Group OIH+U0126 (1.5 nmol),then 0.3 μl of DMSO,U0124 (1.5 nmol),U0126 (0.1 5 nmol,0.45 nmol,1.5 nmol)was given through the catheter separately.PWT and PWL were tested before cathe-terization,at pre-OIH induction,post-OIH induction and 0.5 h after CeA drug administration.After the last test of pain threshold,the rats were sacrificed and CeA tissues were sampled for analyzing the expression of p-ERK by western blot.Results In step 1 compared with control group,PWT and PWL of OIH group were sharply decreased post-OIH induction (P <0.05),concomitant increase of the expression of p-ERK in CeA in OIH group was also observed.In step 2,both PWT and PWL were sharply decreased post-OIH induction (P <0.05).Intra-CeA U0126 injection,but not U0124, reversed both behavioral hyperalgesia and molecular activation of ERK in CeA in a dose-dependent manner (P <0.05).Conclusion ERK plays a pivotal role in the maintenance of fentanyl-induced hy-peralgesia.Targeting inhibition of ERK activation in CeA can alleviate fentanyl-induced hyperalgesia.