The role of sleep problems in central pain processing in rheumatoid arthritis

Yvonne C. Lee, Bing Lu, Robert R. Edwards, Ajay D. Wasan, Nicholas J. Nassikas, Daniel J. Clauw, Daniel H. Solomon, Elizabeth W. Karlson

Research output: Contribution to journalArticlepeer-review

77 Scopus citations


Objective Among rheumatoid arthritis (RA) patients, the intensity of pain may be out of proportion to the severity of peripheral inflammation. This observation suggests that mechanisms of central nervous system pain amplification, such as diminished conditioned pain modulation (CPM), may play a role in enhancing pain perception among some RA patients. This study was undertaken to examine the level of CPM, pressure-pain threshold, and pressure-pain tolerance among RA patients compared to healthy controls. Methods Fifty-eight female RA patients and 54 age-matched female control subjects without chronic pain underwent quantitative sensory testing (QST) to assess CPM levels, pressure-pain thresholds, and pressure-pain tolerance levels. CPM was induced using a cold water bath, and the pain threshold (when patients first felt pain) and pain tolerance (when pain was too much to bear) were assessed with an algometer. Associations between RA and each QST outcome were analyzed using linear regression. Sleep problems, mental health, and inflammation were assessed as mediators of the relationship between RA and QST outcomes. Results The median CPM level was 0.5 kg/cm2 (interquartile range [IQR] -0.1, 1.6) among RA patients, compared to a median of 1.5 kg/cm2 (IQR -0.1, 2.5) among controls (P = 0.04). RA patients, compared to controls, had a lower pain threshold and lower pain tolerance at the wrists (each P ≤ 0.05). In addition, RA patients had greater problems with sleep, pain catastrophizing, depression, and anxiety (P <0.0001 versus controls). Results of mediation analyses suggested that low CPM levels might be attributed, in part, to sleep disturbance (P = 0.04). Conclusion RA patients have impaired CPM when compared to pain-free control subjects. Sleep problems may mediate the association between RA and attenuated CPM.

Original languageEnglish (US)
Pages (from-to)59-68
Number of pages10
JournalArthritis and Rheumatism
Issue number1
StatePublished - Jan 2013
Externally publishedYes

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Rheumatology
  • Pharmacology (medical)


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