Improving pain is a high priority for patients with rheumatoid arthritis (RA). Their pain involves both inflammatory and noninflammatory mechanisms. Research suggests that RA pain is not solely driven by peripheral inflammation, but also involves central nervous system abnormalities in pain regulatory mechanisms, commonly referred to as pain sensitization.
To shed light on the possible interplay between RA disease activity and central pain regulatory mechanisms, Aydemir et al. examined whether improvements in pain sensitization parallel reductions in disease activity when patients with established RA are treated with disease-modifying anti-rheumatic drugs (DMARDs).
Methods
In the study, 182 patients with active RA either initiating or switching DMARD therapy were observed for 12 weeks. To assess pain sensitization, patients underwent quantitative sensory testing, including pressure pain thresholds at multiple anatomic sites, temporal summation at the wrist and forearm, and conditioned pain modulation. Disease activity was measured using the Disease Activity Score 28 with C-reactive protein (DAS28-CRP).
Changes in quantitative sensory testing measures were examined from baseline to week 12, and associations between quantitative sensory testing and disease activity measures were explored using Pearson correlation coefficients and adjusted linear regression analyses.
The Results
Overall, pain sensitivity improved in study patients after 12 weeks of DMARD therapy, and DMARDs were associated with reductions in patient disease activity. Specifically, patients’ pressure pain thresholds significantly increased (i.e., improved) throughout the study period. No statistically significant changes were observed in temporal summation or conditioned pain modulation, measures of central pain regulatory mechanisms.
The researchers found modest—but consistent—associations between reductions in DAS28-CRP scores and increases in pressure pain thresholds at multiple anatomic sites. These findings suggest that improvements in disease activity are associated with reductions in pressure pain sensitivity. Most of these associations remained significant after adjusting for confounders.
For specific components of the DAS28-CRP, a reduction in tender joint count was associated with improvements in pressure pain thresholds at multiple sites. In addition, improvements in pressure pain thresholds at the knees were associated with a reduction in swollen joint counts and improvements in patient global assessment.
For complete details, including source material, refer to the full study.
Excerpted and adapted from:
Aydemir B, Heisler AC, Muhammad LN, et al. Associations between changes in pain sensitization and disease activity following disease-modifying antirheumatic drug therapy in established rheumatoid arthritis. Arthritis Rheumatol. 2025 Dec;77(12).
