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

Abstract

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.

Figure 1

Distribution of conditioned pain modulation levels among rheumatoid arthritis patients and controls.

Figure 2

A. Unadjusted association between RA and conditioned pain modulation (Baron and Kenny criterion #1). B. Mediation analyses showing1) the association between RA and conditioned pain modulation, adjusted for sleep problems and 2) the associations between RA and sleep problems (Baron and Kenny criterion #2) and sleep problems and conditioned pain modulation, adjusted for RA (Baron and Kenny criterion 3#).