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

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    Rheumatoid arthritis patients with high pain, despite minimal joint inflammation, show distinct immune cell profiles. These findings reveal potential new targets for treating centralized pain in rheumatoid arthritis (RA).

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    Area of Science:

    • Immunology
    • Rheumatology
    • Pain Medicine
    • Neuroscience

    Background:

    • Over half of rheumatoid arthritis (RA) patients experience significant pain, even with disease-modifying antirheumatic drug (DMARD) treatment.
    • Emerging evidence suggests centralized or nociplastic pain, beyond joint inflammation, contributes to RA pain.
    • A critical need exists to identify cellular differences in RA patients with centralized pain.

    Purpose of the Study:

    • To characterize the distinct cellular states associated with centralized pain in rheumatoid arthritis (RA) patients.
    • To investigate the relationship between immune cell populations, nociplastic pain, and pain intensity in RA.

    Main Methods:

    • The IMPACT study enrolled 39 RA patients with minimal joint inflammation and varying pain levels.
    • Quantitative sensory testing (QST) assessed nociplastic pain, patient-reported outcome (PRO) surveys captured pain intensity, and blood samples underwent immune profiling.
    • Multi-parameter spectral flow cytometry and single-cell RNA-sequencing (scRNA-seq) analyzed immune cell populations and gene expression.

    Main Results:

    • Supervised and unsupervised analyses identified specific immune cell populations correlated with nociplastic pain and self-reported pain intensity in RA patients.
    • scRNA-seq revealed differences in cell type proportions and gene expression between high and low pain groups.
    • These findings highlight the role of circulating immune cells in altered central nervous system (CNS) pain regulation in RA.

    Conclusions:

    • Circulating immune cells play a significant role in the development and maintenance of centralized pain in rheumatoid arthritis (RA).
    • The study identified specific immune cell signatures associated with nociplastic pain in RA patients.
    • These insights may lead to novel therapeutic strategies targeting immune dysregulation for pain management in RA.