Project 1: Impaired Exercise Induced Hypoalgesia

项目1：运动性痛觉减退 本项目的主要目标是研究与糖尿病相关的神经生物学机制及其影响。 膝关节骨关节炎患者运动性痛觉减退(EIH)。在进行体力活动时， 包括结构化运动在内，是膝盖骨关节炎慢性疼痛患者的一线干预措施，超过一半的患者 的人对运动干预没有反应。一些膝骨性关节炎患者有异常的急性反应。 以疼痛敏感度恶化或无变化为特征的运动，即EIH反应受损。受损的 EIH可能是一线体力活动治疗阴性反应的危险因素 运动，不经意间加剧了剧烈的疼痛。这种EIH受损是否与之前 慢性疼痛患者具有疼痛相关神经系统功能障碍的特征尚不清楚。具体来说， 上行疼痛易化或下行疼痛抑制功能障碍，全身性神经系统增强 敏感度评估自我报告的多感觉敏感度，并改变自主神经系统功能 评估为低心率变异性将被检查为与EIH受损相关的潜在因素。它也不是 已知EIH受损是否代表关键物理(运动诱发的疼痛， 肌肉无力、身体功能受损、体力活动受限)和心理(害怕运动、 对运动的负面看法)膝骨性关节炎患者的损害。这个项目将利用下一个 多中心骨关节炎(MOST)研究的周期综合检测EIH受损程度 一组患有或有膝骨性关节炎风险的成年人，神经系统功能障碍和受损之间的相互关系 以及它们对关键的生理和心理结果的影响。这个项目的第一个目标是确定 神经系统功能障碍，即上行性疼痛易化异常与下行疼痛的关系 抑制、多感官敏感度升高和心率变异性降低到EIH的程度。第二个目标是 检查EIH与运动诱发疼痛、股四头肌力量和身体功能的关系。第三个目标是 评估EIH与运动恐惧、与运动相关的信念和结果预期之间的关系，以及 每天的体力活动。该项目解决了膝盖骨关节炎中有关EIH受损的几个知识空白，最 关节炎是一种常见的疾病，也是全球致残的主要原因。我们将对这两个关系有新的见解 有几个假想的相关机制或标记物和关键的膝骨性关节炎结果。替补第一名- 对于EIH受损的患者，可能需要考虑行疗法，而对于EIH反应强烈的患者，则需要考虑行疗法 对运动干预的反应可能会更好。新的治疗途径可以测试是否潜在的神经紧张 系统损伤被发现是导致EIH受损的原因之一。我们还将对共同的 运动诱发疼痛和对第一线运动管理选项反应不良的观察 随着膝骨性关节炎的出现，最终促进了对膝骨性关节炎治疗新的有针对性的方法的未来研究。

ABSTRACT Project 1: Exercise-Induced Hypoalgesia The overarching objective of this project is to examine the neurobiological mechanisms related to and impact of impaired exercise-induced hypoalgesia (EIH) in people with knee osteoarthritis (OA). While physical activity, including structured exercise, is the first line intervention for people with chronic pain due to knee OA, over half of people do not respond to exercise interventions. Some people with knee OA have an abnormal acute response to exercise characterized by worsened or no change in pain sensitivity, i.e., an impaired EIH response. Impaired EIH may serve as a risk factor for negative response to first-line treatments involving physical activity and exercise, inadvertently exacerbating pain acutely. Whether this impaired EIH is related to previously characterized pain-related nervous system dysfunction in people with chronic pain is not known. Specifically, dysfunction of ascending pain facilitation or descending pain inhibition, heightened generalized nervous system sensitivity assessed self-reported multisensory sensitivity, and altered autonomic nervous system functioning assessed as low heart rate variability will be examined as potential factors related to impaired EIH. It is also not known whether impaired EIH represents the biological underpinnings of key physical (movement-evoked pain, muscle weakness, impaired physical function, limited physical activity) and psychological (fear of movement, negative beliefs about exercise) impairments seen in people with knee OA. This project will leverage the next cycle of the Multicenter Osteoarthritis (MOST) Study to comprehensively examine the degree of impaired EIH in a cohort of adults with or at risk of knee OA, the inter-relations between nervous system dysfunction and impaired EIH, and their impacts on key physical and psychological outcomes. The first aim of this project is to determine the relation of nervous system dysfunction, i.e., abnormalities in ascending pain facilitation and descending pain inhibition, elevated multisensory sensitivity, and low heart rate variability to degree of EIH. The second aim is to examine relation of EIH to movement-evoked pain, quadriceps strength, and physical function. The third aim is to evaluate the relation of EIH to fear of movement, beliefs and outcome expectations related to exercise, and daily physical activity. This project addresses several knowledge gaps about impaired EIH in knee OA, the most common form of arthritis and leading cause of disability worldwide. We will obtain novel insights into the relations of EIH with several hypothesized associated mechanisms or markers and key knee OA outcomes. Alternate first- line therapies may need to be considered for those with impaired EIH, whereas those with strong EIH responses may respond better to exercise interventions. Novel treatment avenues can be tested if the underlying nervous system impairments are found to contribute to impaired EIH. We will also shed new light on the common observation of movement-evoked pain and poor response to first-line exercise management options in people with knee OA, ultimately facilitating future studies of new targeted approaches to knee OA management.