Macaque Model of Carpal Tunnel Syndrome: Effects of Force and Posture Exposures

描述（由申请人提供）：本研究的长期目标是减少与工作有关的腕管综合征（CTS）的发生。在追求这一目标的过程中，我们需要完善我们对工作环境中物理因素（力量，任务持续时间，姿势和重复）对疾病发展的贡献的理解。最终，我们的目标是1）描述各种物理暴露（力量，重复等）与慢性过度使用导致的CTS发展之间的关联; 2）了解损伤和恢复周期; 3）了解物理暴露的修改可以防止CTS发展或复发的程度。我们之前已经开发并使用了一种新的非人类灵长类动物模型来证明慢性过度使用和腕部正中神经病发作之间的直接联系（Dx与CTS密切相关）。在这个应用程序中，我们建议应用这种新的方法来量化选定的工作暴露和疾病发展之间的关系。本申请的具体目的是：1）量化力和腕部姿势在改变CTS的预期发展中的组合效应; 2）量化与CTS的自然恢复相关的恢复期;（3）为扩大猕猴最大随意捏用力数据库，我们用它来预测和设置我们的协议中的力的实验水平（作为最大值的%）。研究设计和方法：将对食蟹猴进行训练，以执行重复的捏取任务，获得每日口粮。将连续测量任务性能数据：施加的力、挤压的数量和持续时间以及挤压之间的间隔。每两周评估一次工作手和非工作手的感觉神经传导速度（SNCV）。将使用纵向组间设计研究捏力和手腕姿势的影响，以表征18周暴露期内各因素对正中神经损伤的影响。累积工作量、损伤程度、至发生时间是将用于表征暴露因素与结局之间关联的一些依赖性指标。将在基线、任务暴露结束时和恢复时收集MRI，以量化神经形态学的变化。较低和较高的暴露水平将使我们能够探索暴露阈值可能位于何处。我们还建议扩大我们的猕猴意志力数据库，这将是未来研究（我们和其他研究团队）的资源。与公共卫生的相关性：CTS在一些工人群体中发生率很高，每例病例的中位数为28个工作日，这使得这对雇员和雇主来说是一种代价高昂的疾病。我们以前的工作证实，CTS可以导致过度使用的手。现在我们需要区分不同的暴露，就神经损伤的程度而言，这样，从长远来看，与工作有关的CTS的发展或复发的风险可以降低。

DESCRIPTION (provided by applicant): The long term objective of this research is to reduce occurrence of work-related Carpal Tunnel Syndrome (CTS). In pursuit of this goal we need to refine our understanding of the contribution of physical factors in the work environment (force, task duration, posture and repetition) to development of the disorder. Ultimately we aim to 1) characterize associations between various physical exposures (force, repetition, etc) and development of CTS due to chronic overuse; 2) understand injury and recovery cycles; and 3) learn the degree to which modification of physical exposures can prevent CTS development or recurrence. We have previously developed and used a new non-human primate model to demonstrate a direct link between chronic overuse and onset of median mononeuropathy at the wrist (Dx closely associated with CTS). In this application we propose to apply this novel approach to quantifying relationships between selected work exposures and disorder development. The specific aims of this application are to: 1) To quantify the combined effects of force and wrist posture in altering the expected development of CTS; 2) To quantify the recovery period associated with a natural recovery from CTS; and 3) To expand our database of maximum voluntary pinch exertion force of the macaque, which we use to predict and set experimental levels of force (as % of maximum) in our protocols. Research design and methods: Macaca fascicularis monkeys will be trained to perform a repetitive pinching task for daily food rations. Task performance data will be measured continuously: force exerted, quantity and duration of pinches, and intervals between pinches. Every two weeks Sensory Nerve Conduction Velocity (SNCV) will be assessed in the working and the non-working hand. Effects of pinch force and wrist posture will be studied using a longitudinal, between group design to characterize effect of each factor on resulting median nerve impairment, over a 18-week exposure period. Cumulative workload, degree of impairment, time to occurrence are some of the dependent measures that will be used to characterize the association between exposure factors and outcomes. MRI will be collected at baseline, at end of task exposure, and at point of recovery, to quantify change in nerve morphology. Low and higher exposure levels will allow us to explore where exposure thresholds might lay. We also propose to expand our database of macaque volitional strength, which will be a resource for future research (ours and other research teams). Relevance to public health: CTS occurs at high rates in some worker populations with a median of 28 lost work days per case, making this a disorder that is costly for employees and employers. Our previous work confirms that CTS can result from overuse of the hands. Now we need to differentiate amongst exposures, in terms of extent of nerve impairment, so that, in the long term, the risk for development or recurrence of work- related CTS can be reduced.