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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Western blotting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150 nmol A-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。
AIM: To investigate the expression of sodium channel NaV1.8 in the membrane of dorsal root ganglion (DRG) neurons of bone cancer rats and its role in bone cancer pain. Methods: First, the rats were randomly divided into PBS saline control group and bone cancer pain group. Western blotting was used to detect the protein expression of NaV1.8 on the cell membrane of DRG neurons in each group. The rats with bone cancer pain were randomly divided into four groups: A-803467 (50 nmol, 100 nmol, and 150 nmol), a blocker of NaV1.8 intrathecally, or its solvent control, Painful effects. Results: (1) The ratio of NaV1.8 band density to internal reference increased from 0.79 ± 0.06 in PBS group to 1.34 ± 0.12 (P <0.01) in bone cancer pain group. (2) Compared with solvent group, intrathecal administration of A-803467 can relieve the mechanical pain and thermal hyperalgesia of bone cancer rats. (3) Slant plate experiments showed that after 150 nmol A-803467 administration, the locomotor activity of bone cancer pain rats was not impaired. CONCLUSION: The expression of NaV1.8 in DRG neurons is significantly increased in bone cancer rats, which may be the basis of peripheral sensitization and bone cancer pain in rats.