Circulating Immune Cells are Associated with Non-Inflammatory Pain in Rheumatoid Arthritis

Over half of patients with rheumatoid arthritis (RA) report clinically meaningful pain, despite treatment with disease-modifying antirheumatic drugs (DMARDs). While joint inflammation is a known cause of pain in patients with rheumatic diseases, emerging data indicate that many patients also suffer from centralized or nociplastic pain. There is a critical unmet need to characterize the altered cellular state that distinguishes patients with centralized pain. In the IMPACT study, 39 RA patients with minimal joint inflammation but varying levels of pain underwent quantitative sensory testing (QST) to assess nociplastic pain, completed patient-reported outcome (PRO) surveys, and provided blood samples for immune profiling. Supervised and unsupervised analysis of the multi-parameter spectral flow cytometry data identified immune cell populations correlated with nociplastic pain and patient-reported pain intensity. Moreover, analyses of single-cell RNA-seq from a subset of 22 patients revealed differences in cell type proportions and differential expression between the high and low pain groups. These studies provide novel insights into the role of circulating immune cells in altered central nervous system (CNS) pain regulation in adults with RA.