Role of autophagy in remifentanil-induced hyperalgesia in rats with incisional pain / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the role of autophagy in remifentanil-induced hyperalgesia in the rats with incisional pain.Methods Forty pathogen-free healthy male Sprague-Dawley rats,aged 2-3 months,weighing 250-280 g,were divided into 5 groups (n =8 each) using a random number tablecontrol group (group C),remifentanil group (group R),incisional pain group (group Ⅰ),incisional pain plus remifentanil group (group IR) and incisional pain plus remifentanil plus autophagy inhibitor 3-methyladenine (3-MA) group (group MA).In group R,remifentanil was infused for 60 min at a rate of 1 μg · kg-1 · min-1 through the caudal vein.In group IR,a 1-cm longitudinal incision was made through skin,fascia and muscle of the plantar aspect of both hindpaws in anesthetized rats at 10 min of remifentanil infusion.In group MA,3-MA 15 mg/kg was injected intraperitoneally at 1 h before establishment of the model,and the other treatments were similar to those previously described in group IR,while the equal volume of normal saline was given in the other groups.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 24 h before infusion and 2,6,24 and 48 h after infusion (T0-4).The rats were sacrificed after the last measurement of pain threshold at T4,and the L4-6 segments of the spinal cord were removed for determination of the expression of microtubule-associated protein 1 light chain 3 Ⅱ (LC3 Ⅱ),Beclin-1 and P62 by Western blot.Results Compared with group C,the MWT was significantly decreased and the TWL was shortened at T1-4 in R,Ⅰ,IR and MA groups,the expression of LC3 Ⅱ and Beclin-1 was up-regulated,and P62 expression was down-regulated in R and IR groups,the expression of LC3 Ⅱ was up-regulated at T4 in group Ⅰ,and the expression of LC3 Ⅱ and Beclin-1 was up-regulated at T4 in group MA (P＜0.0.5).Compared with group R,the MWT was significantly decreased and the TWL was shortened at T1-4,and the expression of LC3 Ⅱ was up-regulated at T4 in group IR (P＜0.05).Compared with group Ⅰ,the MWT was significantly decreased and the TWL was shortened at T1-4,and the expression of LC3 Ⅱ and Beclin-1 was up-regulated and P62 expression was down-regulated at T4 in group IR (P＜0.05).Compared with group IR,the MWT was significantly decreased and the TWL was shortened at T1-4,and the expression of LC3 Ⅱ and Beclin-1 was down-regulated and P62 expression was up-regulated at T4 in group MA (P＜0.05).Conclusion Autophagy is involved in the development and maintenance of remifentanil-induced hyperalgesia in the rats with incisional pain.