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实验性椎间盘突出大鼠自发行为的改变可通过选择性抑制肿瘤坏死因子-α而被阻断。

Changes in spontaneous behavior in rats exposed to experimental disc herniation are blocked by selective TNF-alpha inhibition.

作者信息

Olmarker Kjell, Nutu Magdalena, Størkson Rolf

机构信息

Department of Orthopaedics, Göteborg University, Sahlgrenska University Hospital, Gothenburg, Sweden.

出版信息

Spine (Phila Pa 1976). 2003 Aug 1;28(15):1635-41; discussion 1642. doi: 10.1097/01.BRS.0000083162.35476.FF.

Abstract

STUDY DESIGN

Study of pain behavior in animals by observation of changes in spontaneous behavior.

OBJECTIVES

To assess if selective inhibition of tumor necrosis factor alpha may reduce changes in spontaneous behavior induced by experimental disc herniation in the rat as previously reported.

SUMMARY OF BACKGROUND DATA

It is known that the proinflammatory cytokine tumor necrosis factor alpha may play a key role for the nucleus pulposus-induced nerve dysfunction seen in experimental set ups. However, it is not known if tumor necrosis factor alpha is also involved in pain production induced by the same procedure.

METHODS

Thirty-two rats were used for the study. Twenty-two rats had an L4-L5 disc incision combined with a displacement of the L4 dorsal root ganglion. Twelve of these rats received an intraperitoneal injection of 0.125 mL of 10 mg/mL Remicade, and the remaining 10 were left untreated. Ten rats only had the L4-L5 disc exposed and formed the control group. The day before surgery and days 1, 3, 7, 14, and 21 after surgery, the rats were videotaped from below during a 20-minute period. The duration of four specific behaviors were determined and compared between the three experimental groups at each time point.

RESULTS

Similar to a previous study, the nontreated showed increased signs of focal pain behavior (rotation of the head towards the operated leg and lifting of the operated leg) during the first 7 postoperative days. Treatment with the tumor necrosis factor alpha-inhibitor infliximab significantly reduced this behavior. At day 14, there were no differences between the groups, and at day 21, the nontreated group displayed reduced locomotion and increased immobility, similar to previous observations. Tumor necrosis factor alpha inhibition also seemed to reduce these behaviors.

CONCLUSIONS

The data of the study clearly indicate a role for tumor necrosis factor alpha in the studied behavior changes after experimental disc herniation in the rat. Clinical trials must be performed in order to assess if there may be a clinical use for tumor necrosis factor alpha inhibition in the treatment of sciatica due to disc herniation.

摘要

研究设计

通过观察自发行为变化对动物疼痛行为进行研究。

目的

评估肿瘤坏死因子α的选择性抑制是否如先前报道的那样,可减少大鼠实验性椎间盘突出诱导的自发行为变化。

背景数据总结

已知促炎细胞因子肿瘤坏死因子α可能在实验装置中所见的髓核诱导的神经功能障碍中起关键作用。然而,尚不清楚肿瘤坏死因子α是否也参与由相同手术引起的疼痛产生。

方法

32只大鼠用于该研究。22只大鼠进行L4-L5椎间盘切开术并伴有L4背根神经节移位。其中12只大鼠接受腹腔注射0.125 mL 10 mg/mL英夫利昔单抗,其余10只未接受治疗。10只大鼠仅暴露L4-L5椎间盘,构成对照组。在手术前一天以及手术后第1、3、7、14和21天,在20分钟内从下方对大鼠进行录像。确定三种实验组在每个时间点的四种特定行为的持续时间并进行比较。

结果

与先前的研究相似,未治疗组在术后前7天表现出局部疼痛行为的迹象增加(头部转向手术侧腿和抬起手术侧腿)。用肿瘤坏死因子α抑制剂英夫利昔单抗治疗可显著减少这种行为。在第14天,各组之间没有差异,在第21天,未治疗组表现出运动减少和不动增加,与先前观察结果相似。肿瘤坏死因子α抑制似乎也减少了这些行为。

结论

该研究数据清楚地表明肿瘤坏死因子α在大鼠实验性椎间盘突出后所研究的行为变化中起作用。必须进行临床试验以评估肿瘤坏死因子α抑制在治疗椎间盘突出引起的坐骨神经痛方面是否可能有临床应用。

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