# CNS Pain Mechanisms in Early Rheumatoid Arthritis: Implications for the Acute to Chronic Pain Transition

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2023 · $1,088,912

## Abstract

PROJECT SUMMARY/ABSTRACT
Millions of Americans spend each day in severe pain associated with arthritis. The longer the pain persists, the
harder it is to treat. Efficacious prevention strategies are needed. A major barrier to chronic pain prevention is a
gap in knowledge about how acute joint pain leads to changes in central nervous system (CNS) pathways
responsible for sensing, transmitting and regulating pain. This process, which results in widespread pain
sensitivity, is termed pain centralization. The long-term goal of this research program is to design interventions
to prevent pain centralization, and hence chronic pain, in rheumatoid arthritis (RA). The objective is to identify
modifiable clinical factors and neurobiological pathways that lead to the development of chronic pain in early
RA. The focus of this application is early RA because the first 12 months after RA diagnosis likely represents a
critical time in which to prevent the acute to chronic pain transition. Preliminary data from the Canadian Early
Arthritis Cohort (CATCH) showed that the incidence of fibromyalgia, the prototypical centralized pain condition,
is highest during the first year after RA diagnosis. The central hypothesis is that sleep problems, psychosocial
factors, and abnormal CNS (e.g., brain, spinal cord) regulatory mechanisms predict the development of pain
centralization in the first year after RA diagnosis. The central hypothesis will be tested by pursuing the
following three specific aims: 1) to identify modifiable factors that predict symptoms of pain centralization in
early RA; 2) to identify quantitative sensory testing (QST) evidence of augmented CNS pain processing that
predict symptoms of pain centralization; and 3) to define the functional and anatomic brain pathways
underlying pain centralization in early RA. For the first aim, 534 early RA patients from CATCH and CATCH-
US (US extension of CATCH) will be enrolled to complete measures of sleep, pain, psychosocial factors, and
disability administered at 0, 3, 6 and 12 months after entry into the cohorts. For the second aim, 125 early RA
patients will undergo QST, a type of testing that involves assessing response to well-defined, quantifiable
painful stimuli (e.g., pressure and cold), at 0, 3 and 12 months. For the third aim, 95 patients from Aim 2 will
undergo magnetic resonance imaging at 0 and 12 months to assess neuroimaging markers (e.g., correlations
in activity between different brain regions, volume of tissue in brain areas consisting of nerve cell bodies) that
have previously been shown to be involved in pain centralization. The proposed research is innovative
because it represents a substantive departure from the status quo by: 1) focusing on early RA, 2) incorporating
assessments of pain-related constructs into two multi-site early RA registries, and 3) employing a multimodal
approach, including patient-reported measures of pain, QST, and neuroimaging, to assess pain pathways. The
proposed re...

## Key facts

- **NIH application ID:** 10693840
- **Project number:** 5R01AR064850-10
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Yvonne Claire Lee
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $1,088,912
- **Award type:** 5
- **Project period:** 2013-07-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10693840

## Citation

> US National Institutes of Health, RePORTER application 10693840, CNS Pain Mechanisms in Early Rheumatoid Arthritis: Implications for the Acute to Chronic Pain Transition (5R01AR064850-10). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10693840. Licensed CC0.

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