An Animal Model for Discogenic Low Back Pain

描述（由申请人提供）：腰痛是第二个最常见的症状，需要去看医生。复杂的生物学、生物化学和生物力学现象在腰痛的诊断和治疗中普遍存在。尽管最近的进展，在生物工程的能力，描绘影响临床结果的关键因素，目前的临床决策仍然主要依赖于主观经验，由于缺乏适当的模型来研究这个重要的问题。我们提出了一项为期2年的跨学科试点研究，以开发一种解决长期争议所需的动物模型，即，退行性椎间盘疾病（DDD）和异常力学作为背痛的来源。我们设计了一个综合性的跨学科项目来验证以下假设：1）异常剪切力的应用导致椎间盘及其周围终板和软骨下骨结构的加速退变。2)然而，这些退行性变化本身可能不会引起或引起很少的炎症，其严重程度不足以引起外周和随后的中枢致敏以产生疼痛。3)在已经退化的椎间盘上施加额外的剪切力，或者增强已经存在的炎症，或者产生足以产生疼痛样行为的严重炎症。将使用体内大鼠模型对这些假设进行检验。我们将使用组织学确定椎间盘退变的程度。疼痛感觉将通过疼痛行为测试和脊髓背角浅层中立即早期基因的免疫染色来鉴定。椎间盘内炎症将通过炎性细胞因子的免疫染色来发现，而伤害性神经末梢向内生长到椎间盘中将通过免疫染色技术来定位。

DESCRIPTION (provided by applicant): Low back pain is the second most common symptom necessitating a visit to a physician. Complex biological, biochemical, and biomechanical phenomena pervade both diagnostic and treatment of low back pain. Despite recent advances in bioengineering capabilities to delineate key factors influencing clinical outcomes, current clinical decision making still rests mostly on subjective empirical experience due to the lack of appropriate model for studying this significant problem. We propose a 2-year interdisciplinary pilot study to develope an animal model required for addressing long lasting controversy, i.e., degenerative disc disease (DDD) and aberrant mechanics as a source of back pain. We designed a comprehensive interdisciplinary projects to test the following hypotheses: 1) The application of abnormal shear force induces accelerated degeneration of the intervertebral disc and its surrounding structures of endplates and subchondral bones. 2) These degenerative changes alone, however, may induce no or little inflammation, not severe enough to cause peripheral and consequent central sensitization for generating pain. 3) An additional shear force application on the already degenerated disc either enhances already existing inflammation or generates the severe inflammation enough to generate pain-like behaviors. These hypotheses will be tested using an in vivo rat model. We will determined the degree of disc degeneration using histology. The pain sensation will be identified through the pain behavior test and immunostaining of an immediate early gene in the superficial laminar of the dorsal horn in the spinal cord. Intradiscal inflammation will be found by immunostaining of inflammatory cytokines while the ingrowth of nociceptic nerve endings into the disc will be located by immunostaining techniques.