Orthopaedic Institute, Department of Orthopaedics, The First Affiliated Hospital of SooChow University, 708 Renmin Rd, SuZhou, Jiangsu 215007, PR China; Department of Orthopedics, The Affiliated Peace Hospital of Changzhi Medical College, 110 Yan'an Rd, Changzhi, Shanxi 046000, PR China.
Orthopaedic Institute, Department of Orthopaedics, The First Affiliated Hospital of SooChow University, 708 Renmin Rd, SuZhou, Jiangsu 215007, PR China.
Spine J. 2019 May;19(5):920-930. doi: 10.1016/j.spinee.2018.10.018. Epub 2018 Nov 3.
Previous studies have shown the potential for intervertebral disc tissue regeneration is very limited. While in vivo and in vitro studies have shown that traction can restore disc height and internal pressure, in many clinical studies it was shown that axial mechanical traction for the treatment of low back pain is ineffective.
The aim of this study was to identify how the disc could be distracted, how to define the state of traction, and to further examine the feasibility of regenerating or restoring the degenerative disc by means of traction.
A macro- and microlevel structural analysis of degenerative discs of rat tail before and after controlled immobilization-traction.
In this study, 49 6-month-old male Sprague-Dawley rats were randomly assigned to one of seven groups. Group A was the sham control group in which caudal vertebrae were instrumented with K-wires only. In Group B (model group), caudal vertebrae were immobilized using a custom-made external device to fix four caudal vertebrae (Co7-Co10) and Co8-Co9 underwent 4 weeks of compression to induce moderate disc degeneration. In Group C, vertebrae Co8-Co9 underwent 4 weeks of compression to induce moderate disc degeneration, followed by removal of the external apparatus. Rats in the other four groups (Groups D-G), Co8-Co9 underwent 4 weeks of compression to induce moderate disc degeneration followed by 2 weeks, 4 weeks, 6 weeks, and 8 weeks of distraction, respectively. Caudal vertebrae were harvested and disc height, T2 signal intensity of the discs, disc morphology, total glycosaminoglycan content of the nucleus pulposus and the structure of the Co8-Co9 end plate were evaluated.
After 4 weeks of compression, the intervertebral height and T2 signal intensity of Co8-Co9 vertebrae of rats in Groups B to G were significantly reduced compared with Group A (sham group, all p<.0001). Histological scores of rats in Group B averaged 10.14 and the total glycosaminoglycan (GAG) of nucleus pulposus averaged 238.21μg GAG/ng DNA. The bony end plate structure showed significant changes in comparison with the control Group. After 2 weeks to 8 weeks of traction, the disc space and T2 signal intensity of Co8-Co9 vertebrae in Group E were significantly recovered compared to that of rats in Group B (p<.0001), and the intervertebral height of the Co8-Co9 in Group D, Group F, and Group G when compared with Group B (p<.0001). Meanwhile, the T2 signal intensity of Co8-Co9 in Group D, F, and G when compared with Group B (p<.001). Histological scores dropped from an average of 10.14 in Group B to 5.57 in Group E, and 5.86 in Group F (all p<.0001). Furthermore, the total GAG content of the nucleus pulposus increased from an average of 238.21μg GAG/ng DNA in Group B to 601.02μg GAG/ng DNA in Group E (p<.0001). The number of pores of end plates in rats in Groups D and E both were significantly increased when compared to that of rats in Group B (Groups D vs Groups B, p<.05; Groups E vs Groups B, p<.0001).
A mechanical degenerative model was successfully established by using a custom-made device. We demonstrated that disc degeneration is a cascade of biochemical, mechanical, and structural changes mediated by cells in an abnormal mechanical environment. Not all levels of disc degeneration can be regenerated or repaired. Regeneration or recovery of disc degeneration requires specific conditions. Based on the immobilization-traction mode, the cascade cycle of disc degeneration is interrupted. Traction of 2 to 6 weeks is a sensitive period for regeneration of the degenerative disc. Moreover, the duration and extent of the traction loading must be moderately controllable, and beyond the limits that can lead to significant degeneration. These data may help improve our understanding of the pathogenesis of clinical disc degeneration and how to optimize the use of traction devices for possible regeneration.
先前的研究表明，椎间盘组织再生的潜力非常有限。虽然体内和体外研究表明牵引可以恢复椎间盘高度和内部压力，但在许多临床研究中，轴向机械牵引治疗腰痛是无效的。
本研究旨在确定椎间盘如何被拉开，如何定义牵引状态，并进一步探讨通过牵引再生或修复退行性椎间盘的可行性。
对大鼠尾椎间盘进行控制性固定-牵引前后的宏观和微观结构分析。
在这项研究中，49 只 6 个月大的雄性 Sprague-Dawley 大鼠被随机分配到七个组中的一个。A 组为假对照组，仅用 K 线固定尾椎。B 组（模型组），使用定制的外部设备固定四个尾椎（Co7-Co10），Co8-Co9 经历 4 周的压缩以诱导中度椎间盘退变。C 组，Co8-Co9 经历 4 周的压缩以诱导中度椎间盘退变，然后去除外部设备。其余四个组（D-G 组）的大鼠 Co8-Co9 经历 4 周的压缩以诱导中度椎间盘退变，然后分别进行 2 周、4 周、6 周和 8 周的牵引。收获尾椎，评估椎间盘高度、椎间盘 T2 信号强度、椎间盘形态、髓核总糖胺聚糖含量和 Co8-Co9 终板结构。
在 4 周的压缩后，B 组至 G 组大鼠的 Co8-Co9 椎间盘的椎间高度和 T2 信号强度与 A 组（假对照组）相比显著降低（所有 p<.0001）。B 组大鼠的组织学评分平均为 10.14，髓核的总糖胺聚糖（GAG）平均为 238.21μg GAG/ng DNA。与对照组相比，终板结构发生了显著变化。在 2 周至 8 周的牵引后，E 组大鼠的 Co8-Co9 椎间盘间隙和 T2 信号强度与 B 组相比显著恢复（p<.0001），与 B 组相比，D 组、F 组和 G 组大鼠的 Co8-Co9 椎间高度（p<.0001）。同时，D 组、F 组和 G 组大鼠的 Co8-Co9 的 T2 信号强度与 B 组相比（p<.001）。组织学评分从 B 组的平均 10.14 降至 E 组的 5.57，F 组的 5.86（均 p<.0001）。此外，髓核的总 GAG 含量从 B 组的平均 238.21μg GAG/ng DNA 增加到 E 组的 601.02μg GAG/ng DNA（p<.0001）。与 B 组相比，D 组和 E 组大鼠的终板孔数均显著增加（D 组与 B 组相比，p<.05；E 组与 B 组相比，p<.0001）。
通过使用定制设备成功建立了机械退行性变模型。我们证明椎间盘退变是一种由异常机械环境中介导的生化、力学和结构变化的级联反应。并非所有水平的椎间盘退变都可以再生或修复。椎间盘退变的再生或恢复需要特定的条件。基于固定-牵引模式，椎间盘退变的级联循环被中断。2 至 6 周的牵引是退行性椎间盘再生的敏感时期。此外，牵引加载的持续时间和程度必须适度可控，超出可能导致明显退变的范围。这些数据可能有助于提高我们对临床椎间盘退变发病机制的理解，以及如何优化牵引装置的使用以实现可能的再生。
