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Pain and synovial pathotypes in AMP AIM

AMP AIM 中的疼痛和滑膜病理类型

基本信息

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
项目类别：
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&apos 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

项目摘要

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。的