Department of Orthopaedic Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, HiroshimaHiroshima, 734-8551, Japan.
Department of Orthopaedic Surgery, Miyoshi Central Hospital, Hiroshima, Japan.
Eur Spine J. 2024 May;33(5):2116-2128. doi: 10.1007/s00586-024-08179-9. Epub 2024 Mar 4.
Vertebral endplate lesions (EPLs) caused by severe disk degeneration are associated with low back pain. However, its pathophysiology remains unclear. In this study, we aimed to develop a vertebral EPL rat model mimicking severe intervertebral disk (IVD) degeneration by injecting monosodium iodoacetate (MIA) into the IVDs and evaluating it by assessing pain-related behavior, micro-computed tomography (CT) findings, and histological changes.
MIA was injected into the L4-5 and L5-6 IVDs of Sprague-Dawley rats. Their behavior was examined by measuring the total distance traveled and the total number of rearing in an open square arena. Bone alterations and volume around the vertebral endplate were assessed using micro-CT. Safranin-O staining, immunohistochemistry, and tartrate-resistant acid phosphatase (TRAP) staining were performed for histological assessment.
The total distance and number of rearing times in the open field were significantly reduced in a time-dependent manner. Micro-CT revealed intervertebral osteophytes and irregularities in the endplates at 12 weeks. The bone volume/tissue volume (BV/TV) around the endplates significantly increased from 6 weeks onward. Safranin-O staining revealed severe degeneration of IVDs and endplate disorders in a dose- and time-dependent manner. Calcitonin gene-related peptide-positive nerve fibers significantly increased from 6 weeks onward. However, the number of osteoclasts decreased over time.
Our rat EPL model showed progressive morphological vertebral endplate changes in a time- and concentration-dependent manner, similar to the degenerative changes in human IVDs. This model can be used as an animal model of severe IVD degeneration to better understand the pathophysiology of EPL.
严重椎间盘退变引起的椎体终板损伤（EPL）与下腰痛有关。然而，其病理生理学仍不清楚。在这项研究中，我们旨在通过向椎间盘内注射单碘乙酸（MIA）来建立一种模拟严重椎间盘（IVD）退变的 EPL 大鼠模型，并通过评估与疼痛相关的行为、微计算机断层扫描（CT）发现和组织学变化来对其进行评估。
将 MIA 注入 Sprague-Dawley 大鼠的 L4-5 和 L5-6 椎间盘内。通过测量在开放正方形竞技场中行进的总距离和总竖起次数来检查其行为。使用微 CT 评估椎体终板周围的骨骼改变和体积。进行番红 O 染色、免疫组织化学和抗酒石酸酸性磷酸酶（TRAP）染色以进行组织学评估。
在时间依赖性的情况下，在开放场中行进的总距离和竖起次数明显减少。微 CT 显示在 12 周时出现椎间骨赘和终板不规则。从 6 周开始，终板周围的骨体积/组织体积（BV/TV）显著增加。番红 O 染色显示 IVD 和终板紊乱呈剂量和时间依赖性严重退变。从 6 周开始，降钙素基因相关肽阳性神经纤维明显增加。然而，破骨细胞的数量随着时间的推移而减少。
我们的大鼠 EPL 模型在时间和浓度依赖性方面表现出进行性的形态学椎体终板变化，类似于人类 IVD 的退行性变化。该模型可作为严重 IVD 退变的动物模型，以更好地了解 EPL 的病理生理学。
