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

描述（由申请人提供）： 椎间盘退变和相关的椎间盘源性背痛仍然是主要的国家健康问题。然而，驱动椎间盘退变开始和进展的机制是难以捉摸的，主要是因为识别导致症状表现的早期细胞和分子事件是不可行的。最近出现的啮齿类动物尾椎间盘负荷模型，研究机械应力对椎间盘健康的影响有巨大的潜力，阐明退变的潜在机制。然而，仍有问题的有效性啮齿动物尾盘作为人类光盘的生物力学模拟。我们的中心假设是，啮齿动物尾盘的内部力学类似于人类的光盘。该项目旨在通过测量椎间盘内压力（作为椎间盘内部力学的参数指示）在体外和体内健康和退化的大鼠尾椎间盘来验证这一假设。具体来说，我们提出的工作利用一种新型的微光学传感器来记录椎间盘内的压力在大鼠尾盘，以前不可能获得的数据，由于尺寸的限制。使用体内啮齿动物尾部载荷模型和环形切口损伤模型，我们将表征特定目标1中不同退变阶段椎间盘的椎间盘内压力-外部载荷关系。这些关系从孤立的运动节段，然后可以与人类运动节段的报告，以验证继续使用啮齿动物尾盘模型研究机械应力对椎间盘退变的作用。作为一个相关问题，尚未验证在啮齿动物尾部模型体内施加的载荷是否产生与正常体力活动下人类椎间盘所经历的应力/应变相当的应力/应变。因此，由椎间盘的内部机制控制的细胞刺激水平可能在生理上不准确。特定目标2将在这些动物研究中通常使用的机械负荷方案的应用过程中测量体内大鼠尾椎间盘的椎间盘内压力。测量在体内加载大鼠椎间盘中产生的压力对于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.