Pain and synovial pathotypes in AMP AIM

炎症性关节炎的临床疼痛表型和机制尚不清楚。的 加速药物合作伙伴关系自身免疫和免疫介导的疾病（AMP-AIM）计划 解决了自身免疫性疾病和肿瘤介导的疾病的共同主题， 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 负担是一个未得到满足的主要需求，但不一定与未得到治疗的疟疾有关。疼痛表型，如 如伤害性感受器3ve（3ssue损伤）、伤害性感受器3c（中枢感觉）和神经性疼痛及其 对治疗无反应的贡献构成了一个关键的知识缺口。疼痛是一个核心领域 从风湿性关节炎（RA）、银屑病3c谱系患者的角度评估生活质量 疾病（PSD）、干燥病和系统性红斑狼疮（SLE）。该补充将支持 在RA患者数据收集中增加全面统一的疼痛表型测量 和具有显著滑膜病理学和外周和中枢疼痛敏感性的PSD患者， 与SLE和SJD的协调结果平行。具体来说，我们将1。识别疼痛表型 与疼痛的外周和中枢机制相关，并且在治疗无应答者中， 患者报告的结局（PROMIS 29，2016年纤维肌痛调查）和疼痛计测量的结果 关节特异性痛觉过敏的感觉测试（QST），以评估中枢疼痛 sensi3za3on，2.在RA和PsA滑膜中识别新的疼痛介质， 艾德一种与疼痛相关的基因特征，轴突在此发芽，神经元在此组织上突起。 是最显著的富集途径之一。使用AMP-AIM中获得的滑膜活检，我们 将应用三维染色和容积成像来了解滑膜之间的相互作用， 感觉神经和滑膜细胞类型。这些研究将为疼痛敏感性提供新的见解， 无反应和新的治疗方法。

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.