目的:研究骨癌大鼠背根神经节(dorsal root ganglion,DRG)神经元细胞膜上钠通道Nav1.8的表达及其在骨癌痛中的作用.方法:首先将大鼠随机分为PBS盐水对照组和骨癌痛组,用Westernblotting的方法检测Nav1.8在各组大鼠DRG神经元细胞膜上的蛋白表达.骨癌痛大鼠随机分为四组,鞘内给予Nav1.8的阻断剂A-803467(50 nmol,100 nmol和150 nmol)或其溶剂对照来检测其对骨癌大鼠机械痛敏和热痛敏的影响.结果:(1)Nav1.8的条带密度与内参的比值由PBS组的0.79±0.06上升到骨癌痛组的1.34±0.12 (P<0.01).(2)与溶剂组比,鞘内给予A-803467能够缓解骨癌大鼠的机械痛敏和热痛敏.(3)斜板实验显示给予150nmolA-803467后,骨癌痛大鼠的运动行为未受损.结论:Nav1.8在骨癌大鼠DRG神经元细胞膜上的表达显著升高,这种升高可能是引起骨癌大鼠外周敏化和骨癌痛的基础.
Objective:To investigate the membrane expression of voltage-gated sodium channel Nav 1.8 in the dorsal root ganglion (DRG) neurons in bone cancer rats,and to explore the role of Navl.8 in the development of bone cancer pain.Methods:Rats were randomly divided into two groups:PBS group and MRMT-1 group,and the membrane expression of Navl.8 was detected by Western blotting.The rats with bone cancer pain were divided into four groups:A-803467 (a specific blocker of Navl.8,50 nmol,100 nmol and 150 nmol) groups,or vehicle group.A-803467 or vehicle were injected intrathecally in each group to determine whether blockade of Nav1.8 by A-803467 could alleviate the mechanical allodynia and thermal hyperalgesia in rats with bone cancer pain.Results:(1) The band density ratio of Nav1.8 to internal Control increased from 0.79 ± 0.06 in PBS group to 1.34 ± 0.12 in bone caner pain grouup (P < 0.01).(2) Compared to vehicle,A-803467 significantly alleviated the mechanical allodynia and thermal hyperalgesia in rats with bone cancer pain.(3) The inclined-plate test showed that intrathecal administration of 150 nmol A-803467 had no significant influence on the motor function in rats with bone cancer pain.Conclusion:The membrane expression of Nay1.8 in DRG neurons increased significantly in bone cancer rats.The upregulation of Nav1.8 in DRG neurons likely contributed to the development of peripheral sensitization and the cancer-induced bone pain.