Lillyman David J, Lee Fei San, Barnett Evie C, Miller Tyler J, Alvaro Moreno Lozano, Drvol Henry C, Wachs Rebecca A
Department of Biological Systems Engineering University of Nebraska Lincoln Nebraska USA.
JOR Spine. 2022 Jul 14;5(3):e1212. doi: 10.1002/jsp2.1212. eCollection 2022 Sep.
Chronic low back pain is a global socioeconomic crisis and treatments are lacking in part due to inadequate models. Etiological research suggests that the predominant pathology associated with chronic low back pain is intervertebral disc degeneration. Various research teams have created rat models of disc degeneration, but the clinical translatability of these models has been limited by an absence of robust chronic pain-like behavior. To address this deficit, disc degeneration was induced via an artificial annular tear in female Sprague Dawley rats. The subsequent degeneration, which was allowed to progress for 18-weeks, caused a drastic reduction in disc volume. Furthermore, from week 10 till study conclusion, injured animals exhibited significant axial hypersensitivity. At study end, intervertebral discs were assessed for important characteristics of human degenerated discs: extracellular matrix breakdown, hypocellularity, inflammation, and nerve sprouting. All these aspects were significantly increased in injured animals compared to sham controls. Also of note, 20 significant correlations were detected between selected outcomes including a moderate and highly significant correlation ( = 0.59, < 0.0004) between axial hypersensitivity and disc nerve sprouting. These data support this model as a rigorous platform to explore the pathobiology of disc-associated low back pain and to screen treatments.
慢性腰痛是一个全球性的社会经济危机,部分原因是缺乏合适的模型,导致治疗方法不足。病因学研究表明,与慢性腰痛相关的主要病理是椎间盘退变。多个研究团队已经创建了椎间盘退变的大鼠模型,但这些模型的临床可转化性受到缺乏强烈的慢性疼痛样行为的限制。为了解决这一缺陷,通过在雌性Sprague Dawley大鼠中制造人工环状撕裂来诱导椎间盘退变。随后的退变持续18周,导致椎间盘体积急剧减小。此外,从第10周直到研究结束,受伤动物表现出明显的轴向超敏反应。在研究结束时,对椎间盘进行评估,以确定人类退变椎间盘的重要特征:细胞外基质分解、细胞减少、炎症和神经发芽。与假手术对照组相比,受伤动物的所有这些方面均显著增加。同样值得注意的是,在选定的结果之间检测到20个显著相关性,包括轴向超敏反应与椎间盘神经发芽之间的中度和高度显著相关性(r = 0.59,p < 0.0004)。这些数据支持该模型作为一个严谨的平台,用于探索椎间盘相关性腰痛的病理生物学并筛选治疗方法。