Role of CaMK Ⅱ in primary somatosensory area and hippocampi in reduction of remifentanil-induced hyperalgesia by lidocaine in rats / 中华麻醉学杂志

ABSTRACT

Objective To investigate the role of calcium/calmodulin-dependent protein kinase Ⅱ (CaMK Ⅱ) in the primary somatosensory area (S1 area) and hippocampi in reduction of remifentanil-induced hyperalgesia by lidocaine in rats.Methods One hundred fifty-six male Sprague-Dawley rats,aged 8-10 weeks,weighing 240-260 g,were randomly allocated into 4 groups using a radom number tablecontrol group (group C,n=6),remifentanil group (group R,n=50),lidocaine group (group L,n=50),and remifentanil+lidocaine group (group RL,n =50).Remifentanil was given as a bolus of 6 mg/kg followed by an 2 h infusion of 2.4 μg · kg-1 · min-1 in group R.Lidocaine was given as a bolus of 6 mg/kg followed by an infusion of 200 μg · kg-1 · min-1 for 2 h in group L.In group RL,drug administration was similar to those previously described in R and L groups.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured before administration and at 0.5,2,5 and 24 h after the end of administration.The rats were then sacrificed immediately after administration and at 0.5,2,5 and 24 h after the end of administration in R,L and RL groups,or at the corresponding time point in group C.The S1 area and hippocampi were isolated for determination of phosphorylated CaMK Ⅱ (p-CaMK Ⅱ) expression by Western blot.Results Compared with the value before administration,the MWT was significantly decreased at 0.5 and 2 h after the end of administration (P＜0.05),and no significant change was found in TWL at each time point after the end of administration in R,L and RL groups (P＞0.05).Compared with group C,p-CaMK Ⅱ expression in the S1 area and hippocampi was significantly up-regulated immediately after administration and at 0.5 and 2 h after the end of administration in group R (P＜0.05).Compared with group R,p-CaMK Ⅱ expression in the S1 area and hippocampi was significantly down-regulated immediately after administration and at 0.5 and 2 h after the end of administration in group RL,and p-CaMK Ⅱ expression in the S1 area was significantly down-regulated immediately after administration,and at 0.5 and 2 h after the end of administration,and p-CaMK Ⅱ expression in the hippocampi was down-regulated immediately after administration,and at 0.5,2 and 24 h after the end of administration in group L,and MWT was increased at 0.5 and 2 h after the end of administration in groups L and RL (P＜0.05).There was no significant difference in TWL at each time point among the three groups (P＞0.05).Conclusion The mechanism by which lidocaine mitigates remifentanil-induced hyperalgesia is associated with inhibited activity of CaMKII in the S1 area and hippocampi of rats.