Project 1: Impaired Exercise Induced Hypoalgesia

项目 1：运动损伤引起的痛觉减退

• 批准号: 10555686
• 负责人: TUHINA NEOGI
• 金额: $ 45.33万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2028-02-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10555686
• 关键词: Acute; Acute Pain; Address; Adult; Arthritis; Attention; Autonomic nervous system; Belief; Biological; Central Nervous System; Chronic; Data; Degenerative polyarthritis; Disease; Elderly; Esthesia; Exercise; Fright; Functional disorder; Future; Impairment; Intervention; Knee Osteoarthritis; Knowledge; Light; Mediating; Movement; Muscle Weakness; Nervous System; Nervous System Physiology; Outcome; Pain; Pain Threshold; Pain management; Participant; Patient Self-Report; Persons; Physical Exercise; Physical Function; Physical activity; Physiological; Pilot Projects; Population; Recommendation; Rest; Risk; Risk Factors; Self Assessment; Sensory; Smell Perception; Structure; System; Testing; Touch sensation; Work; adverse outcome; chronic pain; cohort; disability; exercise intervention; exercise prescription; expectation; experience; functional decline; functional outcomes; heart rate variability; improved; insight; multisensory; neurobiological mechanism; novel; novel strategies; osteoarthritis pain; pain inhibition; pain processing; pain reduction; pain sensitivity; psychologic; psychological outcomes; quadriceps muscle; response; sound; targeted treatment

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.

摘要项目1：麻醉诱导的痛觉减退 该项目的总体目标是研究与神经生物学机制相关的影响， 膝骨关节炎（OA）患者运动诱发痛觉减退（EIH）受损。虽然体力活动， 包括结构化运动，是膝关节OA所致慢性疼痛患者的一线干预措施， 的人对运动干预没有反应。有些人与膝关节OA有异常的急性反应 以疼痛敏感性恶化或没有变化为特征的运动，即，EIH反应受损受损 EIH可能是对涉及体力活动的一线治疗产生负面反应的风险因素， 锻炼，无意中加剧了疼痛。这种受损的EIH是否与先前的 慢性疼痛患者的特征性疼痛相关神经系统功能障碍尚不清楚。具体地说， 上行性疼痛易化或下行性疼痛抑制功能障碍，全身神经系统增强 敏感性评估自我报告的多感觉敏感性，并改变自主神经系统功能 被评估为低心率变异性的患者将作为与EIH受损相关的潜在因素进行检查。也不 已知受损的EIH是否代表关键的身体（运动诱发的疼痛， 肌肉无力、身体功能受损、身体活动受限）和心理（害怕运动， 对运动的消极信念）在膝关节OA患者中观察到的损伤。该项目将利用下一个 多中心骨关节炎（MOST）研究的一个周期，以全面检查 一组患有膝关节骨性关节炎或有膝关节骨性关节炎风险的成年人，神经系统功能障碍和受损 EIH及其对关键生理和心理结果的影响。本项目的第一个目标是确定 神经系统功能障碍，即，上行性疼痛易化和下行性疼痛异常 抑制，多感觉敏感性升高，心率变异性降低至EIH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、信念和与运动相关的结果预期的关系，以及 日常身体活动。该项目解决了关于膝关节OA中EIH受损的几个知识缺口， 关节炎是一种常见的关节炎，也是全球残疾的主要原因。我们将获得对关系的新见解 EIH与几种假设的相关机制或标志物和关键膝关节OA结局的关系。第一个候补- 对于EIH受损的患者，可能需要考虑一线治疗，而对于EIH反应较强的患者， 可能会对运动干预做出更好的反应。新的治疗途径可以测试，如果潜在的神经 系统损伤被发现有助于受损EIH。我们还将对共同的 观察运动诱发疼痛和对一线运动管理选择反应不良的人群 与膝关节OA，最终促进未来的研究新的有针对性的方法，膝关节OA的管理。