Relationship between hippocampal CREB/BDNF signaling pathway and cognitive dysfunction in rats with chronic pathological pain / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the relationship between hippocampal cyclic adenosine monophosphate response element-binding protein(CREB)/brain-derived neurotrophic factor(BDNF)signaling pathway and cognitive dysfunction in rats with chronic pathological pain.Methods Thirty-two healthy adult male Sprague-Dawley rats,weighing 220-250 g,were divided into 3 groups using a random number tablecontrol group(group C,n=8),sham operation group(group S,n=8)and chronic pathological pain group(group CP,n=16).Chronic pathological pain model was established by injecting cobra venom 0.4 mg(4 μl)into the sheath of the infraorbital nerve.The mechanical pain threshold was measured at 3 days before establishment of the model(baseline)and 4 days and 1,2,3,4 and 8 weeks after establishment of the model.Morris water maze test was performed to evaluate the spatial learning and memory abilities at 5 and 9 weeks after establishment of the model.Eight rats were sacrificed at 5 and 9 weeks after establishment of the model in CP group,and rats were sacrificed after the end of Morris water maze test at 9 weeks after establishment of the model in C and S groups.The hippocampi were isolated for determination of the expression of phosphorylated CREB and BDNF in the hippocampal tissues using Western blot.Results Compared with group C,the mechanical pain threshold was significantly decreased at each time point after establishment of the model,the escape latency was prolonged at 5 and 9 weeks after establishment of the model,the rate of time of staying at the target quadrant was decreased,the frequency of crossing the original platform was decreased,and the expression of phosphorylated CREB and BDNF was down-regulated at 9 weeks after establishment of the model in group CP(P0.05).Conclusion The mechanism underlying cognitive dysfunction may be related to inhibited activation of CREB/BDNF signaling pathway in the hippocampus of rats with chronic pathological pain.