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.

项目概要 中风后肩部疼痛极为常见，30-70% 的患者都会出现肩部疼痛。慢性中风后 肩痛 (PSSP) 会导致抑郁、干扰运动恢复并降低生活质量。 尽管 PSSP 被认为是由肩关节周围肌筋膜组织损伤引起的，但 PSSP 肌筋膜功能障碍和疼痛的病理生理学尚未阐明，导致漏诊 早期诊断和疼痛管理取得不同成功的机会。透明质酸的积累 肌肉及其筋膜中的酸（HA）可导致肌筋膜功能障碍。 HA 是一种糖胺聚糖 (GAG) 和 肌肉细胞外基质的主要成分。在生理量中，它起到润滑剂和 粘弹性减震器，在肌肉收缩和伸展过程中实现力传递。减少关节 活动性和痉挛可导致肌肉中 HA 的局灶性积累和改变，从而导致 绷紧带的形成、深筋膜和肌肉层的功能失调、运动范围缩小 （ROM）和疼痛。肌肉 HA 浓度可使用 T1rho (T1ρ) MRI 和肌筋膜成像 可以使用定量超声上的回声纹理分析和剪切应变映射来评估功能障碍 （美国），这可能作为有用的生物标志物来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 量化 GAG/HA 积累的程度 麻痹性与非麻痹性肩旋转肌，并将 T1ρ MRI 测量值与 US 回波相关联 质地测量，开发临床友好的工具来推断 HA 积累的程度；和（2） 使用相同肌肉的 US 剪切应变图来区分潜在 PSSP 和主动 PSSP 肩关节被动外旋（ER）时，麻痹侧与非麻痹侧进行比较，即 与 PSSP 密切相关。为了进入 R33 阶段，我们将证明具有统计学意义的 (1) 使用 T1ρ MRI 的 GAG/HA 积累，以及 (2) 潜在和活性剪切应变图的差异 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来 在肌内 (IM) 透明质酸酶注射以增加无痛效果的临床试验中监测治疗反应 被动肩部 ER-ROM。我们将注射人重组透明质酸酶或生理盐水 功能失调的肩带肌肉，并测量无痛肩部 ER-ROM（主要结果）(1) 注射前，(2) 注射后 1-2 周（主要终点）和 (3) 注射后 6-8 周。我们期望 局部注射透明质酸酶会分解积累的 HA，从而增加无痛肩部 ER， 并且这种改进将与定量 MRI 和 US 成像指标相关。其结论是，这 该提案将开发肌筋膜功能障碍的定量成像生物标志物，以监测对肌筋膜功能障碍的反应 治疗并与 NIH HEAL Initiative 保持一致，以加强研究以加强疼痛管理。