Pain and synovial pathotypes in AMP AIM

在fl炎症性关节炎3中，临床疼痛的表型和机制尚不清楚。这个 加速3 ng药物伙伴自身免疫和免疫介导性疾病(AMP-AIM)计划 讨论自身免疫和fl炎症介导的疾病的共同主题，以及理解 疼痛的复杂性和影响以及患者和医生感知的疾病之间的分离 负担，不一定与未在fl中治疗有关，是一个主要的未得到满足的需求。疼痛表型，如 伤害性疼痛、神经炎症性疼痛和神经病理性疼痛。 对治疗无反应的贡献包括严重的知识缺口。疼痛是一个核心领域 类风湿性关节炎(RA)患者生活质量的ff分析 精神障碍(PSD)、干燥综合征和系统性红斑狼疮(SLE)。本增刊将支持 在现有的类风湿关节炎数据收集中增加全面而统一的疼痛表型测量 和PSD患者，有突出的滑膜病理和周围和中枢疼痛敏感。 与系统性红斑狼疮和系统性红斑狼疮的协调eff治疗平行。特别是fi，我们将1.识别疼痛表型 与疼痛的外周和中枢机制有关，在治疗中无反应，使用这两种方法 Pa3ent报告的结果(Promis 29,2016 Fibromyalgia Survey)和止痛计测量的Quan3ta3ve 以斜方肌为参照评估中枢性疼痛的关节特异性fic痛觉过敏 在RA和PSA滑膜中建立在工作基础上的新的疼痛介质 fi发现了一个与疼痛相关的基因标志，其中轴突发芽和神经元在组织上投射 是最重要的fi丰富途径之一。使用AMP-AIM获得的滑膜活检，我们 将应用三维染色和体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提供新的见解， 无反应，以及新的治疗方法。

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.