Open Access Highly Accessed Open Badges Research article

Enhanced reactivity to pain in patients with rheumatoid arthritis

Robert R Edwards12*, Ajay D Wasan1, Clifton O Bingham3, Joan Bathon3, Jennifer A Haythornthwaite2, Michael T Smith2 and Gayle G Page4

Author Affiliations

1 Department of Anesthesiology, Harvard Medical School, Brigham & Women's Hospital, 850 Boylston Street, Suite 302, Chestnut Hill, MA 02467, USA

2 Department of Psychiatry, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Baltimore, MD 21287, USA

3 Division of Rheumatology, Johns Hopkins University School of Medicine, 5200 Eastern Avenue, MFL Suite 4100, Baltimore, MD 21224, USA

4 Johns Hopkins University School of Nursing, 525 N. Wolfe Street, Baltimore, MD 21287, USA

For all author emails, please log on.

Arthritis Research & Therapy 2009, 11:R61  doi:10.1186/ar2684

See related editorial by Straub and Kalden,

Published: 4 May 2009



Maladaptive physiological responses to stress appear to play a role in chronic inflammatory diseases such as rheumatoid arthritis (RA). However, relatively little stress research in RA patients has involved the study of pain, the most commonly reported and most impairing stressor in RA. In the present study, we compared psychophysical and physiological responses to standardized noxious stimulation in 19 RA patients and 21 healthy controls.


Participants underwent a single psychophysical testing session in which responses to a variety of painful stimuli were recorded, and blood samples were taken at multiple time points to evaluate the reactivity of cortisol, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) to the experience of acute pain.


The findings suggest that RA patients display a fairly general hyperalgesia to mechanical and thermal stimuli across several body sites. In addition, while serum cortisol levels did not differ at baseline or following pain testing in patients relative to controls, the RA patients tended to show elevations in serum IL-6 and demonstrated enhanced pain-reactivity of serum levels of TNF-α compared with the healthy controls (P < 0.05).


These findings highlight the importance of pain as a stressor in RA patients and add to a small body of literature documenting amplified responses to pain in RA. Future studies of the pathophysiology of RA would benefit from the consideration of acute pain levels when comparing RA patients with other groups, and future trials of analgesic interventions in RA patients may benefit from evaluating the effects of such interventions on inflammatory activity.