Pain and synovial pathotypes in AMP AIM

AMP AIM 中的疼痛和滑膜病理类型

• 批准号: 10856445
• 负责人: Jennifer Howitt Anolik
• 金额: $ 30.73万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-22 至 2026-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10856445
• 关键词: 3-Dimensional; Acceleration; Acute Pain; Address; Administrative Supplement; Affect; Afferent Neurons; Arthritis; Autoimmune; Autoimmune Diseases; Axon; Biopsy; Cells; Cellular Indexing of Transcriptomes and Epitopes by Sequencing; Clinical; Collection; Coupled; Data; Data Collection; Disease; Dissociation; Enrollment; Fatigue; Fibroblasts; Fibromyalgia; Functional disorder; Gene Expression; Genomics; Goals; Hyperalgesia; Image; Immune; Inflammation; Inflammatory; Inflammatory Arthritis; Injury; Joints; Knowledge; Lead; Light; Measures; Mediating; Mediator; Medicine; Mental Depression; Microscopy; Molecular; Molecular Profiling; Musculoskeletal Diseases; Neurites; Neuronal Plasticity; Neurons; Nociception; Numeric Rating Scale; Oranges; Outcome; Pain; Pain Measurement; Pain Origin; Pain Research; Pain Threshold; Pain intensity; Pain interference; Pathology; Pathway interactions; Patients; Peripheral; Phenotype; Physicians; Psoriasis; Psoriatic Arthritis; Quality of life; Reporting; Research; Research Personnel; Residual state; Rheumatism; Rheumatoid Arthritis; Sensory; Site; Sjogren' s Syndrome; Sleep disturbances; Stains; Surveys; Synovial Cell; Synovial Membrane; Systemic Lupus Erythematosus; Technology; Testing; Therapeutic; Time; Tissues; Translational Research; United States National Institutes of Health; Work; afferent nerve; associated symptom; axonal sprouting; base; burden of illness; cell type; central pain; central sensitization; chronic pain; clinical pain; clinical phenotype; cohort; data integration; diagnostic criteria; experience; genetic signature; high dimensionality; improved; innovation; insight; nerve supply; novel; novel therapeutic intervention; pain patient; pain symptom; painful neuropathy; patient subsets; peripheral pain; pressure; programs; sample fixation; social health determinants; tissue injury; transcriptomics; trapezius muscle; treatment response

Clinical pain phenotypes and mechanisms in inflammatory arthri3s are poorly understood. The Accelera3ng Medicines Partnership Autoimmune and Immune-Mediated Disease (AMP-AIM) Program addresses common themes across autoimmune and inflammatory-mediated diseases, and understanding the complexity and impact of pain and the dissocia3on between pa3ent and physician perceived disease burden, not necessarily related to untreated inflamma3on, is a major unmet need. Pain phenotypes such as nocicep3ve (3ssue injury), nociplas3c (central sensi3za3on), and neuropathic pain and their contribu3on to therapeu3c non-response cons3tutes a cri3cal knowledge gap. Pain is a core domain affec3ng quality of life from the perspec3ve of pa3ents with Rheumatoid Arthri3s (RA), Psoria3c Spectrum Disorder (PSD), Sjögren’s disease, and Systemic Lupus Erythematosus (SLE). This supplement will support adding comprehensive and uniform measurements of pain phenotyping to exis3ng data collec3on in RA and PSD pa3ents with prominent synovial pathology and both peripheral and central pain sensi3za3on, in parallel with the harmonized efforts in SLE and SJD. Specifically, we will 1. Iden3fy pain phenotypes associated with peripheral and central mechanisms of pain and in treatment non-responders, using both pa3ent reported outcomes (PROMIS 29, 2016 Fibromyalgia Survey) and algometer measured Quan3ta3ve Sensory Tes3ng (QST) of joint-specific hyperalgesia with a trapezius reference to assess central pain sensi3za3on, 2. Iden3fy novel mediators of pain in the RA and PsA synovium building on work that iden3fied a gene signature correla3ng with pain, where axon sprou3ng and neuron projec3on organiza3on were among the most significantly enriched pathways. Using synovial biopsies obtained in AMP-AIM, we will apply 3-dimensional staining and volume imaging to understand the interac3ons between synovial sensory nerves and synovial cell types. These studies will provide novel insights into pain sensi3za3on, non-response, and new treatment approaches.

炎症性关节炎的临床疼痛表型和机制尚不清楚。 Accelera3ng 药物合作伙伴自身免疫和免疫介导疾病 (AMP-AIM) 计划 共同探讨自身免疫性疾病和炎症介导疾病的主题，并理解 疼痛的复杂性和影响以及患者和医生感知疾病之间的分离 负担，不一定与未经治疗的炎症有关，是未满足的主要疼痛表型需求。 如 nocicep3ve（3ssue 损伤）、nociplas3c（中枢 sensi3za3on）和神经性疼痛及其 治疗无反应构成了关键的知识差距。疼痛是一个核心领域。 从类风湿性关节炎 (RA)、银屑病谱系患者的角度来看，它们对生活质量的影响 该补充剂将支持疾病 (PSD)、干燥病和系统性红斑狼疮 (SLE)。 在 RA 现有数据收集中添加全面且统一的疼痛表型测量 具有明显滑膜病变以及外周和中枢疼痛感觉的 PSD 患者， 与 SLE 和 SJD 的协调一致，我们将 1. 识别疼痛表型。 与疼痛的外周和中枢机制以及治疗无反应者相关，使用两者 患者报告的结果（PROMIS 29，2016 年纤维肌痛调查）和海藻计测量的 Quan3ta3ve 以斜方肌为参考的关节特异性痛觉过敏的感觉测试 (QST)，用于评估中枢性疼痛 sensi3za3on, 2. 基于以下工作，确定 RA 和 PsA 滑膜中新型疼痛介质 确定了与疼痛相关的基因特征，其中轴突萌发和神经元投射组织 是最显着富集的途径之一，我们使用 AMP-AIM 中获得的滑膜活检样本。 将应用 3 维染色和体积成像来了解滑膜之间的相互作用 这些研究将为疼痛感觉提供新的见解， 无反应和新的治疗方法。