Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, Seoul 135-896, Republic of Korea.
Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, Seoul 135-896, Republic of Korea.
Spine J. 2021 Jun;21(6):1031-1041. doi: 10.1016/j.spinee.2021.01.014. Epub 2021 Jan 16.
Lumbar intervertebral disc herniation (LDH) is a common disease that causes low back pain, radiating leg pain, and sensory impairment. Preclinical studies rely heavily upon standardized animal models of human diseases to predict clinical treatment efficacy and to identify and investigate potential adverse events in human subjects. The current method for making the LDH model involves harvesting the nucleus pulposus (NP) from autologous coccygeal discs and applying to the lumbar nerve roots just proximal to the corresponding dorsal root ganglion. However, this surgical method generates a model that exhibits very different characteristics of disc herniation than that observed in human.
To produce a rat LDH model that better resembles disc herniation in humans and a standardized and uniform LDH model using Interleukin-1 beta (IL-1β).
Experimental rat LDH model.
We exposed the L5-6 disc dorsolaterally on the right side through hemi-laminectomy without nerve compression. Herniation was initiated by puncturing the exposed disc with a 30-gauge needle at a depth of 4 mm. Interleukin-1 beta (IL-1β) was injected simultaneously to heighten the pathological processes of disc degeneration, including inflammatory responses, matrix destruction, and herniation of the NP. We performed histological staining to assess morphological changes, immunohistochemistry to analyze inflammation- and pain-related expression within and around the puncture site of the L5-6 disc, and real-time polymerase chain reaction to examine expression of markers for degenerative processes. In addition, we performed locomotor tests on the rats.
We found that the IL-1β groups showed that the border between the annulus fibrosis and nucleus pulposus was severely interrupted compared to that of the control (puncture only) group. And, the injection of IL-1β leads to accelerated disc degeneration and inflammation in a more consistent manner in LDH model. Functional deficit was consistently induced by puncturing and injection of IL-1β in the exposed disc.
The method proposed here can be used as an index to control the severity of disc degeneration and inflammation through the injected IL-1β concentration concurrent with surgically induced herniation.
Our proposed model may facilitate research in drug development to evaluate the efficacy of potential therapeutic agents for disc herniation and neuropathic pain and may also be used for nonclinical studies to more accurately assess the effectiveness of various treatment strategies according to the severity of disc degeneration.
腰椎间盘突出症（LDH）是一种常见的疾病，会引起腰痛、放射状腿痛和感觉障碍。临床前研究主要依赖于人类疾病的标准化动物模型，以预测临床治疗效果，并识别和研究人类受试者中的潜在不良反应。目前，制作 LDH 模型的方法是从自体尾骨椎间盘采集髓核（NP），并将其应用于与相应背根神经节近端相邻的腰椎神经根。然而，这种手术方法产生的模型与人类观察到的椎间盘突出症的特征非常不同。
利用白细胞介素-1β（IL-1β）制作更类似于人类椎间盘突出症的大鼠 LDH 模型，并制作标准化、统一的 LDH 模型。
大鼠 LDH 模型的实验研究。
通过半椎板切除术从右侧 L5-6 椎间盘背外侧暴露，不进行神经压迫。通过用 30 号针头在 4 毫米深度穿刺暴露的椎间盘来启动突出。同时注射白细胞介素-1β（IL-1β）以增强椎间盘退变的病理过程，包括炎症反应、基质破坏和 NP 突出。我们进行了组织学染色以评估形态学变化，免疫组织化学分析穿刺部位内和周围的炎症和疼痛相关表达，实时聚合酶链反应（PCR）检测退行性过程的标志物表达。此外，我们对大鼠进行了运动测试。
我们发现，与仅穿刺组相比，IL-1β 组的纤维环和髓核之间的边界严重中断。并且，IL-1β 的注射以更一致的方式加速了 LDH 模型中的椎间盘退变和炎症。在暴露的椎间盘上穿刺和注射 IL-1β 可始终如一地引起功能缺陷。
这里提出的方法可以作为通过注射的 IL-1β 浓度与手术诱导的突出同时控制椎间盘退变和炎症严重程度的指标。
我们提出的模型可能有助于药物开发研究，以评估潜在治疗药物对椎间盘突出症和神经病理性疼痛的疗效，也可用于非临床研究，根据椎间盘退变的严重程度更准确地评估各种治疗策略的效果。
