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

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2022 · $235,127

## 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 strategies to manage and prevent chronic pain 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 is termed pain
centralization. The long-term goal of this research program is to enable patients with arthritis and
musculoskeletal diseases to function physically, cognitively, and emotionally without impairment from chronic
pain. The objective of this STAR award is to identify brain pathways associated with the development of
chronic pain in patients with rheumatoid arthritis (RA). The focus of this application is on patients who have had
symptoms of RA for less than 12 months. The rationale for this is based on preliminary data from the Canadian
Early Arthritis Cohort showing that the incidence of fibromyalgia, the prototypical centralized pain condition, is
highest during the first year after RA diagnosis. Thus, it is hypothesized that the first 12 months after RA
diagnosis may represent a critical time during which the acute to chronic pain transition may be prevented.
Therefore, the specific aims of this STAR award are to: 1) identify neurotransmitters in the brain that will predict
the development of chronic pain during the first year after RA symptom onset, and 2) identify measures of the
microstructural integrity of nerve fibers in the brain that will predict the development of chronic pain in the first
year after RA symptom onset. To assess neurotransmitter levels, proton magnetic resonance spectroscopy will
be performed on a subgroup of 80 participants undergoing magnetic resonance imaging as a part of Aim 3 of
the parent R01. Proton magnetic resonance spectroscopy is a non-invasive test for measuring biochemical
changes in the brain. To assess the microstructural integrity of the nerve fibers in the brain, diffusion tensor
imaging will be performed on the same subgroup of 80 participants. Diffusion tensor imaging is a brain imaging
technique that measures the magnitude and direction of water molecule movements in the nerve fibers of the
brain. The proposed research is innovative because it represents a substantive departure from the status quo
by: 1) focusing on early RA, 2) incorporating two novel brain imaging methods that drill down to the level of
specific neurotransmitters and nerve fiber tracts (as opposed to larger brain regions, typically assessed by
structural and functional magnetic resonance imaging), and 3) employing a multimodal approach, including
patient-reported measures of pain, objective assessments of pain sensitivity, and brain imaging, to assess pain
pathways. The proposed research is significant because it will enable us to expand our research program by
rigorously im...

## Key facts

- **NIH application ID:** 10520450
- **Project number:** 3R01AR064850-09S1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Yvonne Claire Lee
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $235,127
- **Award type:** 3
- **Project period:** 2013-07-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10520450

## Citation

> US National Institutes of Health, RePORTER application 10520450, CNS Pain Mechanisms in Early Rheumatoid Arthritis: Implications for the Acute to Chronic Pain Transition (3R01AR064850-09S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10520450. Licensed CC0.

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