Biomarker of Tissue Tolerance and Behavior in a Rat Model of WMSD

与工作相关的肌肉骨骼疾病占失去工作时间疾病的30%，然而， 随着时间的推移，其发生和持续的病理生理机制还不完全。 明白了。这项工作的长期目标是使用一种创新的上肢过度使用损伤模型 大鼠识别和表征组织变化和行为后遗症的细胞机制 与重复的和/或有力的伸展有关。该项目的具体目标是： 1)确定长期暴露于两种任务方案的机制， 重复-低力(MRLF)和高重复-高力(HRHF)，导致骨吸收和病理 改变和关节软骨损伤，如果这些改变背后的机制是炎症的， 机械过度使用，或者两者兼而有之。 2)确定长期暴露于两种任务方案的机制，MRLF和 HRHF会导致肌腱和神经组织的纤维化和病理变性，如果 这些变化背后的机制是炎症或机械过度使用，或两者兼而有之。 3)确定组织变化的生物标志物与感觉运动之间是否存在关系 在两种任务方案，MRLF和HRHF暴露后的功能。 将训练大鼠在MRLF(每分钟8个到达)执行自愿到达和抓取任务 @5%最大自愿拉力(MPF)或HRHF(在60%MPF时达到每分钟12)。二 实验组将接受抗肿瘤坏死因子α或白细胞介素1受体拮抗剂 为了阻止炎症而预防性的。肌肉骨骼组织、周围神经和血清 使用后测试分析组织炎症和变性的细胞和生化标志物 对照组设计。正中神经功能也将使用测试后对照组进行测试和分析 设计。将分析指示伸展性能和运动协调的行为变量 使用重复测量设计随时间变化。为了确定血清和血清与 行为变量方面，将采用多元回归分析。两个试验组将执行以下任一操作 MRLF或HRHF任务16或22周。在每周的终点，所有的动物都将接受感觉运动 性能测试，然后将被随机分为3个小组进行显微镜检查，蛋白质 分析和正中神经传导速度测试(每个分析类型每组5-10次，每周一次 端点)。年龄、饮食和体重相匹配的训练有素的对照组将在匹配的时间点被牺牲 与实验动物相比。前肢组织将以双边方式收集并准备用于各种 分析这些实验将增强我们对长期暴露于 组织和功能上的风险因素(重复和力)以及机制(机械)的组合 超负荷或炎症诱导的分解代谢/纤维化)导致这些反应(变性、疼痛和 功能丧失)。

Work-related musculoskeletal disorders account for 30% of lost work time illnesses, yet, the pathophysiological mechanisms underlying their development and persistence over time is incompletely understood. The long term goal of this work is to use an innovative model of upper limb overuse injury in the rat to identify and characterize cellular mechanisms underlying tissue changes and behavioral sequelae associated with the performance of repetitive and/or forceful reaching. The specific aims for this project are: 1) To determine the mechanisms whereby long-term exposure to two task regimens, medium repetition-low force (MRLF) and high repetition-high force (HRHF), leads to bone resorption and pathological changes, and articular cartilage damage, and if the mechanism underlying these changes is inflammatory, mechanical overuse, or both. 2) To determine the mechanisms whereby long-term exposure to two task regimens, MRLF and HRHF, leads to fibrosis and pathological degeneration in musculotendinous and neural tissues and if the mechanism underlying these changes is inflammatory, mechanical overuse, or both. 3) To determine if there is a relationship between biomarkers of tissue changes and sensorimotor function after exposure to two task regimens, MRLF and HRHF. Rats will be trained to perform a voluntary reaching and grasping task at MRLF (8 reaches per minute @ 5% maximum voluntary pulling force, MPF), or HRHF (12 reaches per minute at 60% MPF). Two experimental groups will receive either anti-tumor necrosis factor alpha or interleukin-1 receptor antagonist prophylactically in order to block inflammation. Musculoskeletal tissues, peripheral nerve and serum will be analyzed for cellular and biochemical markers of tissue inflammation and degeneration using a post-test control group design. Median nerve function will be tested and analyzed also using a post-test control group design. Behavioral variables indicative of reach performance and movement coordination will be analyzed for changes over time using a repeated measures design. To determine the association between serum and behavioral variables, a multiple regression analysis will be used. The 2 experimental groups will perform either the MRLF or HRHF task for 16 or 22 weeks. At each weekly endpoint, all animals will undergo sensorimotor performance testing and will then be split randomly into 3 subgroups for microscopic examination, protein analysis and median nerve conduction velocity testing (n=5-10 per group per analysis type at all weekly endpoints). Trained controls, matched by age, diet, and weight, will be sacrificed at matched time points for comparison to experimental animals. Forelimb tissues will be collected bilaterally and prepared for the various analyses These experiments will enhance our understanding of the effects of long-term exposure to combinations of risk factors (repetition and force) on tissue and function, as well as mechanisms (mechanical overload, or inflammation-induced catabolism/fibrosis) underlying those responses (degeneration, pain and loss of function).