摘要
目的建立大鼠骨癌痛模型并观察电压依赖性钠通道Nav1.8在其背根神经节(DRG)的表达,以探讨Nav1.8在癌症性疼痛中的作用。方法在雌性SD大鼠左胫骨内注射Walker256细胞(103/μl、104/μl、105/μl)后1、3、5、7、10、14天观察机械痛敏阈值和CO2激光热痛敏阈值的变化,与对照组大鼠进行比较,分析癌痛组大鼠出现痛阈降低的时间。于接种细胞后14天取双侧胫骨做病理切片观察肿瘤生长情况。RT-PCR检测癌痛组及对照组大鼠L5～L6DRGNav1.8基因的表达。结果所有接种Walker256细胞的大鼠均可见胫骨内实质性肿瘤的膨胀性生长和严重的骨质重构。各癌痛组大鼠分别于第7～14天出现进行性加重的疼痛行为学改变,其左侧(癌痛侧)DRGNav1.8的表达明显升高(P<0.05),对侧的表达与对照组之间无明显差异。结论胫骨内注射Walker256细胞的大鼠在产生浸润性生长的骨肿瘤同时,可伴进行性的痛觉过敏,是骨转移瘤相关疼痛研究可靠的动物模型。Nav1.8基因在骨癌痛模型大鼠DRG中的表达水平上调,提示该通道可能参与骨癌痛的发生过程。
Objective To establish a model of bone cancer pain in rats and to evaluate the role of voltage gated sodium channel Nav1. 8 in the course of bone cancer pain by observing the expression of Nav1. 8 in dorsal root ganglion in the model with bone cancer pain. Method Female SD rats received intra-tibial injection of syngenetic Walker256 mammary gland carcinoma cells in different concertration （10^3/μl、10^4/μl or 10^5/μl）. Pain threshold of mechanical hyperalgesia and thermal hyperalgesia were tested at ld, 3d, 5d, 7d, 10d, and 14d triter cell injection. The development of the bone tumor was verified by pathological examination 14d after cell injection. The L5-6 DRG was obtained from normal rats and rats with bone cancer pain. Expression of voltage gated sodium channel Nav1. 8 was investigated by RT-PCR. Result Intra-tibial injection of Walker256 cells produced a rapidly expanding tumor within the boundaries of the tibia, causing marked remodeling of the bone. Rats receiving intra-tibial injection of Walker256 cells displayed gradual development of both mechanical and thermal hyperalgesia 7-14 days after the injection. The expression of Nav1. 8 in DRG was up-regulated in the model of bone cancer pain in rats （P〈0.05）. The increases were seen ipsilaterally. Conclusion Rats received intra-tibial injection of Walker256 cells displayed a expanding tumor within the tibia, as well as a gradual development of hyperalgesia which provided a valid model for pain associated with bone metastases. Bone cancer pain resulted in an up-regulation in the expression of Nav1. 8 in DRG, suggesting Nav1. 8 may contribute to bone cancer pain.
出处
《解放军医学杂志》
CAS
CSCD
北大核心
2007年第4期319-322,共4页
Medical Journal of Chinese People's Liberation Army
基金
国家自然科学基金资助项目(30300327)
