Measuring intradiscal pressure during degeneration in rat discs using a fiber opt

描述(由申请人提供)： 椎间盘退变和与之相关的椎间盘源性背痛仍然是国家的主要健康问题。然而，驱动椎间盘退变的启动和进展的机制尚不清楚，主要是因为识别导致症状出现的早期细胞和分子事件是不可行的。最近出现的研究机械应力对椎间盘健康影响的啮齿类动物尾盘负荷模型在阐明退变的潜在机制方面具有巨大的潜力。然而，啮齿动物尾盘作为人类盘的生物力学类似物的有效性仍然存在疑问。我们的中心假设是，啮齿动物尾盘的内部机制类似于人类的尾盘。该项目旨在通过在体外和体内测量健康和退变的大鼠尾盘的盘内压力来验证这一假说。具体地说，我们提出的工作利用一种新型的微型光学传感器来记录大鼠尾盘中的盘内压力，这是以前由于尺寸限制而无法获得的数据。利用在体鼠尾部负荷模型和环状切开损伤模型，我们将针对特定的目的1表征不同退变阶段椎间盘的内压-外负荷关系。然后将从单独运动节段获得的这些关系与已报道的人类运动节段的关系进行比较，以验证继续使用啮齿动物尾盘模型来研究机械应力对椎间盘退变的作用。作为一个相关的问题，在活体啮齿类动物尾巴模型中施加的载荷尚未被证实会产生与正常身体活动下人类关节盘所经历的应力/应变相当的应力/应变。因此，由椎间盘内部机制控制的细胞刺激水平在生理上可能并不准确。特殊目的2将在这些动物研究中通常使用的机械加载方案的应用过程中，在活体测量大鼠尾盘内的压力。在体内测量加载的大鼠盘中产生的压力将对未来动物和细胞培养模型的实验设计至关重要。

DESCRIPTION (provided by applicant): Intervertebral disc degeneration and associated discogenic back pain continue to represent major national health concerns. However, the mechanisms that drive the initiation and progression of disc degeneration are elusive, mainly because identifying the early cellular and molecular events leading to the presentation of symptoms is not feasible. Rodent tail disc loading models that have recently emerged to study the effects of mechanical stress on disc health have vast potential for elucidating the underlying mechanisms of degeneration. However, there remain questions as to the validity of rodent tail discs as a biomechanical analogue of human discs. Our central hypothesis is that the internal mechanics of rodent tail discs are similar to those of human discs. This project aims to test this hypothesis by measuring intradiscal pressures - as a parameter indicative of internal disc mechanics - in healthy and degenerate rat caudal discs both in vitro and in vivo. Specifically, our proposed work utilizes a novel micro-optical sensor to record intradiscal pressure in rat tail discs, data that have not previously been possible to obtain due to size constraints. Using an in vivo rodent tail loading model and an annular incision injury model, we will characterize intradiscal pressure-external load relationships of discs at various stages of degeneration in Specific Aim 1. These relationships obtained from isolated motion segments can then be compared with those reported for human motion segments in order to validate the continued use of rodent tail disc models for studying the role of mechanical stress on disc degeneration. As a related concern, the loads applied in rodent tail models in vivo have not been verified to produce stress/strain that is comparable to that experienced by human discs under normal physical activity. Thus, the level of cellular stimulation governed by the internal mechanics of the disc may not be physiologically accurate. Specific Aim 2 will measure intradiscal pressure in rat tail discs in vivo during the application of mechanical loading regimens typically used in these animal studies. Measuring the pressures generated in loaded rat discs in vivo will be crucial for future experimental design for both animal and cell culture models.