Evaluating the role of fascia structure and innervation in chronic knee OA pain

总结 为了提高我们对慢性肌肉骨骼疼痛的理解和治疗，NOT-AR-23 - 015呼吁 风湿性、皮肤和肌肉骨骼疾病疼痛研究的扩展。针对这一NOSI，我们建议 扩大我们的家长奖，以评估肌筋膜对慢性OA疼痛和残疾的贡献。母 奖项-UC2AR082196-是RE-JOIN联盟的一部分，其首要目标是定义 不同关节和关节周围组织的感觉神经支配。在这个联盟范围内的目标，中央 我们的父母奖的目的是定义联合神经支配模式的变化，并评估这些神经支配如何 这些变化与临床前模型和患者中症状性关节疼痛和残疾的发展有关。 除了关节结构（骨、滑膜、软骨、纤维软骨）的神经支配外，慢性OA疼痛可能 由关节外发生的生理变化驱动，包括外关节筋膜的变化， 关节肌筋膜有丰富的神经支配，筋膜神经支配或结构的病理变化可 扰乱感觉信息并导致OA疼痛。我们使用超声成像支持的初步数据 这些发现，如筋膜厚度、肌肉回声和筋膜硬度的变化， 有症状的膝关节OA患者整体关节疼痛更严重，功能更差。因此，本补充 申请旨在扩大家长奖的目的，增加新的研究筋膜的作用， 慢性膝关节OA的发展。UC2研究提供了一个非凡的和时间敏感的机会， 了解筋膜结构和神经支配是如何相关的，以及筋膜的病理变化如何导致 OA相关疼痛和膝关节残疾。我们建议在收集的数据中测试以下假设 通过母公司奖项招募的膝关节OA患者队列：1）筋膜结构（厚度、组成、刚度） 在膝关节OA和无OA对照个体之间存在差异，并与疼痛和功能相关; 2） 筋膜神经支配模式（感觉）在膝关节OA和无OA对照个体之间存在差异， 与疼痛和功能相关; 3）筋膜结构和神经支配模式将随年龄而变化。这些 将使用阔筋膜超声成像（B型，剪切波弹性成像）评价假设， 全膝关节置换术时收集的阔筋膜活检分析。患者疼痛和功能将 在关节成形术前进行评估，如母公司裁决中所述。结合起来，这些数据将使我们能够比较 临床相关的超声图像，以微观结构的变化，在筋膜，而有关所有这些措施 筋膜病理的定量指标的疼痛和残疾的OA患者。

Summary To improve our understanding and treatment of chronic musculoskeletal pain, NOT-AR-23-015 calls for an expansion of rheumatic, skin, and musculoskeletal disease pain research. In response to this NOSI, we propose to expand our parent award to evaluate myofascial contributions to chronic OA pain and disability. The parent award - UC2AR082196 - is part of the RE-JOIN Consortium, which has the over-arching goal of defining the sensory innervation of different articular and peri-articular tissues. Within this Consortium-wide goal, the central objective of our parent award is to define shifts in joint innervation patterns and evaluate how these innervation shifts relate to the development of symptomatic joint pain and disability in both preclinical models and patients. In addition to the innervation of joint structures (bone, synovium, cartilage, fibrocartilage), chronic OA pain may be driven by physiologic shifts occurring beyond the joint, including changes in the fascia that lines the extra- articular muscle. Fascia is richly innervated, and pathological changes in the fascia innervation or structure could disrupt sensory information and contribute to OA pain. Our preliminary data using ultrasound imaging support these findings, as variations in fascial thickness, muscle echogenicity and fascia stiffness are associated with greater overall joint pain and worse function in persons with symptomatic knee OA. As such, this supplement application seeks to expand the aims of the parent award by adding new studies on the role of fascia on the development of chronic knee OA. The parent UC2 study provides an extraordinary and time-sensitive opportunity to understand how fascia structure and innervation are related and how pathologic shifts in fascia contribute to OA-related pain and disability in the knee. We propose to test the following hypotheses in data collected from a cohort of knee OA patients, recruited via the parent award: 1) Fascia structure (thickness, composition, stiffness) will vary between individuals with knee OA and OA-free controls and be associated with pain and function; 2) Fascia innervation patterns (sensory) will vary between individuals with knee OA and OA-free controls, and be associated with pain and function; and 3) Fascia structure and innervation patterns will vary across age. These hypotheses will be evaluated using ultrasound imaging of fascia lata (b-mode, shear wave elastography) and analyses of fascia lata biopsies collected at the time of total knee arthroplasty. Patient pain and function will be assessed prior to arthroplasty, as described in the parent award. Combined, these data will allow us to compare clinically-relevant ultrasound images to microstructure changes in the fascia, while relating all of these measures of fascia pathology to quantitative metrics of pain and disability in OA patients.