Effect of verapamil on expression of K+·Cl-cotransporter 2 in spinal dorsal horns during remifentanil-induced hyperalgesia in a rat model of incisional pain / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effect of verapamil on the expression of K+-Cl-cotransporter 2 (KCC2) in spinal dorsal horns during remifentanil-induced hyperalgesia in a rat model of incisional pain.Methods Thirty-two pathogen-free healthy adult male Sprague-Dawley rats,aged 6-7 weeks,weighing 250-300 g,were divided into 4 groups (n=8 each) using a random number table:control group (group C),incisional pain group (group Ⅰ),incisional pain plus remifentanil plus verapamil group (group I+R+ V) and incisional pain plus remifentanil group (group I+R).Normal saline was subcutaneously infused in group C.A 1 cm long incision was made in the plantar surface of the right hindpaw in anesthetized rats in group Ⅰ.Verapamil 5 mg/kg was intraperitoneally injected at 10 min before establishment of the incisional pain model in group I+R+V.In I+R and I+R+V groups,the model of incisional pain was established,and remifentanil was subcutaneously infused for 30 min at a rate of 80 μg · kg-1 · h-1 simultaneously.The mechanical paw withdrawal threshold (MWT) to yon Frey filament stimulation was measured at 1 day before establishment of the model (T0) and 2,6,24 and 48 h after establishment of the model (T1-4).The rats were sacrificed after measurement of MWT at T4,and the lumbar enlargement segments of the spinal cord were harvested for determination of the expression of KCC2 by immunofluorescence.Results Compared with group C,the MWT was significantly decreased at T1-4,and the expression of KCC2 was down-regulated in the other groups (P＜0.05).Compared with group Ⅰ,the MWT was significantly decreased at T1-4,and the expression of KCC2 was down-regulated in group I+R (P＜0.05).Compared with group I+R,the MWT was significantly increased at T1-4,and the expression of KCC2 was up-regulated in group I+R+V (P＜0.05).Conclusion The mechanism by which verapamil reduces remifentanil-induced hyperalgesia is related to up-regulation of the expression of KCC2 in spinal dorsal horns in a rat mnodel of incisional pain.