An Animal Model for Discogenic Low Back Pain

描述(由申请人提供)：腰痛是第二种最常见的症状，需要去看医生。复杂的生物、生化和生物力学现象普遍存在于腰痛的诊断和治疗中。尽管最近在描述影响临床结果的关键因素的生物工程能力方面取得了进展，但由于缺乏适当的模型来研究这一重大问题，目前的临床决策仍然主要依赖于主观经验。我们建议进行一项为期两年的跨学科试点研究，以开发一种动物模型，以解决长期存在的争议，即退行性间盘疾病(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检验以下假设：1)异常剪切力的施加会导致终板和软骨下骨的椎间盘及其周围结构加速退变。2)然而，这些单独的退行性改变可能不会或很少引起炎症，不够严重，不足以引起外周和随后的中枢敏化，从而产生疼痛。3)在已经退变的椎间盘上施加额外的剪切力，要么加剧已经存在的炎症，要么产生严重的炎症，足以产生疼痛样行为。这些假说将通过活体大鼠模型进行验证。我们将通过组织学来确定椎间盘退变的程度。痛感将通过疼痛行为测试和脊髓背角浅层即刻早期基因的免疫染色来识别。炎症细胞因子的免疫染色将发现椎间盘内的炎症，而伤害性神经末梢进入椎间盘的位置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.