Pain behavior and the expression of phosphorylated cAMP response element binding protein and brain-derived neurotrophic factor in dorsal horn of spinal cord in a mouse model of bone cancer pain

Abstract

Objective To investigate the role of phosphorylated cyclic-AMP response element binding protein (pCREB) and brain-derived neurotrophic factor (BDNF) in bone cancer pain,via observing the change of pain behavior and the expression of pCREB and BDNF in dorsal horn of spinal cord.Methods A total of 52 male mice (C3H/HeJ) were randomly divided into tumor group (group T,n=26)and sham group (group S,n=26).In group T,bone cancer pain was induced by implantation 20 μl of α-minimal essence medium (α-MEM) containing osteosarcoma cells into the intramedullary space of right femur.In group S,20 μl culture medium α-MEM containing no cancer cells was injected instead.Pain behavior of animals in both groups was assessed by the spontaneous lifting times (SLTs) and paw withdrawal mechanical threshold (PWMT) measured at 1 day before and at 4,7,10,14 d,and 21 d after inoculation.Another 3 mice were sacrificed at the corresponding time point and the L3-5 spinal cords were obtained for determining the expressions of pCREB and BDNF by western blotting.Results Compared with preoperative base level,the levels of SLTs in group S were significantly increased at 7,10,14,21 d after inoculation,the obvious increasing of SLTs [(4.43±0.91),(7.10±1.03),(11.27 ±1.35),(13.03 ±0.58),respectively] (P＜0.05),at 10,14,21 d after inoculation,the significant decreasing of PWMT[(0.63±0.20),(0.32±0.12),(0.24±0.12) g] were observed in group T (P＜0.05) and the expressions of pCREB[(3.78±0.58),(3.92±0.46),(4.92±0.37)] and BDNF [(2.13±0.31),(2.88±0.15),(2.58±0.41)] in group T were obviously increased (P＜0.05).Conclusions The expressions of pCREB and BDNF in dorsal horns of spinal cords were increased in a mouse model of bone cancer pain,accompanied by the pain behavior,suggesting spinal cord pCREB and BDNF may be involved in the development and maintenance of bone cancer pain in mice. Key words: Bone cancer pain; Mice; Phosphorylated cAMP response element binding protein; Brain-derived neurotrophic factor; Dorsal horn of spinal cord