Quantifying and Treating Myofascial Dysfunction in Post Stroke Shoulder Pain

量化和治疗中风后肩痛的肌筋膜功能障碍

• 批准号: 10571306
• 负责人: PREETI RAGHAVAN
• 金额: $ 146.23万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-21 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10571306
• 关键词: Area; Articular Range of Motion; Biological Markers; Chronic; Clinic; Clinical Trials; Cumulative Trauma Disorders; Deep Fascia; Development; Disaccharides; Early Diagnosis; Extracellular Matrix; Fascia; Functional disorder; Glucuronic Acids; Glycosaminoglycans; Helping to End Addiction Long-term; Human; Hyaluronic Acid; Hyaluronidase; Image; Injections; Intramuscular; Joint structure of shoulder region; Lead; Lubricants; Magnetic Resonance Imaging; Measurement; Measures; Mental Depression; Monitor; Muscle; Muscle Contraction; Normal saline; Pain; Pain management; Pain-Free; Painless; Paresis; Patients; Pattern; Phase; Physiological; Placebos; Polymers; Prevention; Public Health; Quality of life; Recombinants; Relaxation; Research; Rotation; Severities; Shock; Shoulder; Shoulder Pain; Side; Stretching; Testing; Texture; Time; Tissues; Ultrasonography; United States National Institutes of Health; follow-up; hydrophilicity; imaging biomarker; improved; infraspinatous muscle; joint mobilization; motor recovery; muscle stiffness; opioid misuse; opioid use disorder; outcome prediction; pectoralis major muscle; post stroke; primary endpoint; primary outcome; quantitative imaging; quantitative ultrasound; response; spasticity; success; tool; transmission process; treatment response; ultrasound; viscoelasticity

PROJECT SUMMARY Shoulder pain is extremely common after stroke and occurs in 30-70% of patients. Chronic post stroke shoulder pain (PSSP) contributes to depression, interferes with motor recovery, and decreases quality of life. Although PSSP is thought to be caused by damage to the myofascial tissues around the shoulder joint, the pathophysiology of myofascial dysfunction and pain in PSSP has not been elucidated, leading to missed opportunities for early diagnosis and variable success with pain management. The accumulation of hyaluronic acid (HA) in muscle and its fascia can cause myofascial dysfunction. HA is a glycosaminoglycan (GAG) and a chief constituent of the extracellular matrix of muscle. In physiologic quantities, it functions as a lubricant and a viscoelastic shock absorber, enabling force transmission during muscle contraction and stretch. Reduced joint mobility and spasticity can result in focal accumulation and alteration of HA in muscle, leading to the development of taut bands, dysfunctional gliding of deep fascia and muscle layers, reduced range of motion (ROM), and pain. Muscle HA concentrations can be imaged using T1rho (T1ρ) MRI, and myofascial dysfunction can be assessed using echo texture analysis and shear strain mapping on quantitative ultrasound (US), which may serve as useful biomarkers to elucidate the pathophysiology of myofascial dysfunction in PSSP. Hence, in the R61 phase we will: (1) Quantify the extent of GAG/HA accumulation using T1ρ MRI in the paretic versus non-paretic shoulder rotator muscles, and correlate the T1ρ MRI measurements with US echo texture measurements to develop a clinic-friendly tool to infer the extent of HA accumulation; and (2) Distinguish between latent versus active PSSP using US shear strain mapping of the same muscles on the paretic side compared with the non-paretic side during passive shoulder external rotation (ER), which is strongly associated with PSSP. To proceed to the R33 phase, we will demonstrate a statistically significant difference in (1) GAG/HA accumulation using T1ρ MRI, and (2) shear strain mapping for latent and active PSSP using quantitative US. In the R33 phase, we will use the imaging metrics identified in the R61 phase to monitor treatment response in a clinical trial of intramuscular (IM) hyaluronidase injections to increase pain-free passive shoulder ER-ROM. We will administer human recombinant hyaluronidase or normal saline injections in the dysfunctional shoulder girdle muscles, and measure pain-free shoulder ER-ROM (primary outcome) (1) pre-injection, (2) 1–2 weeks post-injection (primary endpoint) and (3) 6-8 weeks post-injection. We expect that local hyaluronidase injections will breakdown the accumulated HA leading to increased pain-free shoulder ER, and that the improvement will correlate with quantitative MRI and US imaging metrics. At its conclusion, this proposal will develop quantitative imaging biomarkers of myofascial dysfunction to monitor response to treatment and aligns with the NIH HEAL Initiative to bolster research to enhance pain management.

项目摘要 肩痛是中风后非常常见的，发生在30-70%的患者中。慢性卒中后 肩痛（PSSP）会导致抑郁，干扰运动恢复，并降低生活质量。 虽然PSSP被认为是由肩关节周围的肌筋膜组织损伤引起的， PSSP中肌筋膜功能障碍和疼痛的病理生理学尚未阐明，导致遗漏 早期诊断的机会和疼痛管理的可变成功。透明质酸的积累 肌肉及其筋膜中的酸（HA）可引起肌筋膜功能障碍。HA是糖胺聚糖（GAG）， 肌肉细胞外基质的主要成分。在生理量，它的功能作为润滑剂和 粘弹性减震器，使肌肉收缩和伸展过程中的力传输。降低关节 活动性和痉挛状态可导致HA在肌肉中的局部积聚和改变， 发展拉紧带，深筋膜和肌肉层的滑动功能障碍，活动范围减少 (ROM)和痛苦。肌肉HA浓度可以使用T1 rho（T1ρ）MRI成像，肌筋膜 功能障碍可以使用定量超声上的回波纹理分析和剪切应变图来评估 (US)，这可能是有用的生物标志物，以阐明肌筋膜功能障碍的病理生理学， PSSP。因此，在R61阶段，我们将：（1）使用T1ρ MRI定量GAG/HA蓄积的程度， 轻瘫与非轻瘫肩旋转肌，并将T1ρ MRI测量值与US回波相关联 质地测量，以开发一种临床友好的工具来推断HA积累的程度;以及（2） 使用相同肌肉的US剪切应变图区分潜伏性与活动性PSSP， 在被动肩外旋（ER）过程中，麻痹侧与非麻痹侧相比， 与PSSP密切相关。为了进入R33阶段，我们将证明一个统计学上显著的 （1）使用T1ρ MRI的GAG/HA蓄积和（2）潜伏性和活动性的剪切应变图的差异 PSSP使用定量US。在R33阶段，我们将使用R61阶段确定的成像指标， 在肌内（IM）透明质酸酶注射的临床试验中监测治疗反应，以增加无痛性 被动肩关节ER-ROM。我们将给予人重组透明质酸酶或生理盐水注射， 功能失调的肩带肌肉，并测量无痛肩部ER-ROM（主要结局）（1） 注射前，（2）注射后1-2周（主要终点）和（3）注射后6-8周。我们预计 局部透明质酸酶注射将分解累积的HA导致增加的无痛肩部ER， 并且该改善将与定量MRI和US成像度量相关。最后，这 一项提案将开发肌筋膜功能障碍的定量成像生物标志物，以监测对 治疗，并与NIH HEAL倡议保持一致，以加强研究，以加强疼痛管理。