Objective To evaluate the role of calcium/calmodulin-dependent kinase Ⅱ alpha (CaMK Ⅱα) in the central nucleus of the amygdale (CeA) in fentanyl-induced hyperalgesia in rats and the relationship with miniature excitatory postsynaptic currents (mEPSCs).Methods Thirty-two male Sprague-Dawley rats,weighing 50-80 g,in which the CeA was successfully cannulated,were randomly divided into 4 groups (n=8 each) using a random number table:control 1 group (group C1),fentanylinduced hyperalgesia 1 group (group FIH1),KN92 group,and KN93 group.Normal saline was injected subcutaneously,and dimethyl sulfoxide (DMSO) was given into the amygdale in group C1.In group FIH1,fentanyl was injected subcutaneously (60 μg/kg per time,4 times in total,15-min interval,cumulative dose of 240 μg/kg) to establish the model of hyperalgesia.In KN92 and KN93 groups,KN92 and KN93 10 nmol were given into the CeA after establishing the model.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal threshold (TWT) were measured at 6 and 7 h after fentanyl or normal saline injection.Another 12 Sprague-Dawley rats were selected and randomly divided into either control 2 group (group C2) or fentanyl-induced hyperalgesia 2 group (group FIH2) using a random number table with 6 rats in each group.The brains were removed and sliced 12 h later,and the frequency and amplitude of mEPSCs were recorded.KN93 10 nmol was then added to the artificial cerebral spinal fluid,and the frequency and amplitude of mEPSCs were recorded by whole cell patch-clamp technique.Results Compared with group C 1,the MWT and TWT were significantly decreased at 6 h after fentanyl or normal saline injection in FIH1,KN92 and KN93 groups,and at 7 h after fentanyl or normal saline injection in FIH and KN92 groups (P＜0.05).Compared with group FIH1,the MWT and TWT were significantly increased at 7 h after fentanyl or normal saline injection in group KN93 (P＜0.05),and no significant change was found in group KN92 (P＞0.05).Compared with group C2,the frequency and amplitude of mEPSCs were significantly increased before administration of KN93 (P ＜ 0.05),and no significant change was found in the frequency and amplitude of mEPSCs after administration of KN93 in group FIH2 (P＞0.05).Compared with the value before KN93 administration,no significant change was found in the frequency and amplitude of mEPSCs after administration of KN93 in group C2 (P＞0.05),and the frequency and amplitude of mEPSCs were significantly decreased after administration of KN93 in group FIH2 (P＜ 0.05).Conclusion Activation of CaMK Ⅱ α in the CeA enhances synaptic excitation in neurons,which is involved in fentanyl-induced hyperalgesia in rats.