江苏大学学报（医学版）2015，Vol.25Issue(1)：33-37,5.DOI:10.13312/j.issn.1671-7783.y140300
鞘内注射肿瘤坏死因子-α单克隆抗体缓解大鼠骨癌痛的机制
Intrathecal injection of TNF-α antibodies attenuates bone cancer pain in rats
陆向荣 1王枫 1魏金荣 2周友浪 2缪秀华 3肖颖 2徐为袁3
作者信息
- 1. 江苏大学附属昆山医院手外科,江苏昆山215300
- 2. 苏州大学神经科学研究所,江苏苏州215123
- 3. 苏州大学附属张家港第一人民医院骨科,江苏张家港215600)
- 折叠
摘要
Abstract
Objective:To investigate the analgesic effect of TNF-α monoantibodies on the development of bone cancer pain in rats and its possible mechanism involved.Methods:Thirty-two (n =32) normal female Sprague-Dawley rats weighting 180-200 g were randomly divided into 4 groups (n =8 for each group):sham operation group,bone cancer pain group,TNF-α monoantibody group and vehicle group.The rat model of bone cancer pain was induced by injection of breast cancer cells (Walker 256) 10 μL (2× 107cell) into the left proximal tibia bone marrow cavity.Sham operation group was injected by 10 μL normal saline.On the 1 1th day after inoculation,TNF-α monoantibody group received intrathecal injection of 8 μL TNF-α monoantibodies (etanercept) once daily for consecutive 7 days.The vehicle group received 8 μL intrathecal injection of normal saline solution for consecutive 7 days,while the rest two groups without intrathecal injection.Mechanical pain threshold was measured before inoculation and on day 1,4,7,10,14,17 after inoculation.On day 17 after inoculation,the left side dorsal root ganglion (DRG,L2 to L5) were harvested to detect the expression of voltage-gated sodium channel Nav 1.8.Results:Compared with sham operation group,the mechanical pain threshold began to decline on day 7 after inoculation and significantly decreased on day 10 after inoculation in bone cancer pain group (P ＜0.05).On day 17,Nav 1.8 in the DRGs of bone cancer pain group expressed significantly higher than it in sham operation group (P ＜0.05); On day 11 the mechanical pain threshold increased dramatically in TNF-α antibody group,reached peak at 2 h after drug injection and returned to baseline level at 8 h (P ＜0.01).The behavioristics change was similar to the first dose,but the increase of the mechanical pain threshold was decreased after repeated injection for 7 days.On day 17 the expression of Nav1.8 in TNF-α monoantibody group was much lower than it in the control group (P ＜ 0.01).Conclusion:The TNF-α monoantibody reduced bone cancer pain which may be through inhibiting the high expression of Nay1.8 in DRG.关键词
骨癌痛/背根神经节/肿瘤坏死因子-α/电压门控钠离子通道1.8Key words
bone cancer pain/dorsal root ganglion/TNF-α/voltage-gated sodium channel Nav 1.8分类
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陆向荣,王枫,魏金荣,周友浪,缪秀华,肖颖,徐为袁..鞘内注射肿瘤坏死因子-α单克隆抗体缓解大鼠骨癌痛的机制[J].江苏大学学报（医学版）,2015,25(1):33-37,5.
