Role of AMPK-dependent autophagic signaling pathway in ketamine-induced reduction of diabetic neuropathic pain in rats / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the role of AMP-activated protein kinase (AMPK)-dependent autophagic signaling pathway in ketamine-induced reduction of diabetic neuropathic pain (DNP) in rats.Methods Sixty male Wistar rats,aged 3 months,weighing 200-250 g,were equally randomized into 5 groups using a random number tablecontrol group (C group),normal saline group (NS group),ketamine group (K group),ketamine + Compound C group (KC group),and ketamine + 3-methyladenine (3-MA) group (KM group).DNP model was established by intraperitoneal injection of streptozocin (STZ)65 mg/kg in anesthetized rats.Four weeks later,the equal volume of normal saline,ketamine 10 mg/kg,ketamine 10 mg/kg + Compound C1 mg/kg,and ketamine + 3-MA 2 μl were injected intraperitoneally once a day for 7 consecutive days in NS,K,KC and KM groups,respectively.The mechanical paw withdrawal threshold (MWT) was measured on 8th day.The rats were then sacrificed,and the lunbar segment (L1-5) of the spinal cord was removed for determination of the expression of AMPKαt,Beclin-1,microtubule-associated protein 1 light chain (LC) 3B (by Western blot) and dendritic spine density in the dorsal root ganglia.Results Compared with group C,the MWT,expression of AMPKα,Beclin-1,and LC3B,and dendritic spine density were significantly decreased in group NS (P＜0.05).Compared with group NS,the MWT,expression of AMPKαt,Beclin-1,and LC3B,and dendritic spine density were significantly increased in group K (P＜0.05).Compared with group K,the MWT,expression of AMPKα,Beclin-1,and LC3B,and dendritic spine density were significantly decreased in KC and KM groups (P＜0.05).Conclusion Activation of AMPK-dependent autophagic pathway is involved in ketamine-induced reduction of DNP in rats.