An Animal Model for Discogenic Low Back Pain

椎间盘源性腰痛的动物模型

• 批准号: 7130511
• 负责人: TAE-HONG LIM
• 金额: $ 7.38万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-01 至 2008-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7130511
• 关键词: backache; model; pain

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.

描述（由申请人提供）：腰痛是第二常见的症状，需要去看医生。复杂的生物学、生物化学和生物力学现象遍及腰痛的诊断和治疗。尽管最近生物工程技术在描述影响临床结果的关键因素方面取得了进展，但由于缺乏研究这一重大问题的适当模型，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2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终板和软骨下骨的周围结构加速退变。2)然而，这些退行性改变本身可能不会引起炎症或很少引起炎症，其严重程度不足以引起外周和随后的中枢致敏，从而产生疼痛。3)对已经退变的椎间盘施加额外的剪切力，要么增强已经存在的炎症，要么产生严重的炎症，足以产生类似疼痛的行为。这些假设将在体内大鼠模型中得到验证。我们将通过组织学来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的即时早期基因的免疫染色来识别。椎间盘内炎症可通过免疫染色发现，而向椎间盘内生长的伤害神经末梢可通过免疫染色技术定位。