Background/Purpose:   Among rheumatoid arthritis (RA) patients, pain may exist out of proportion to peripheral inflammation.  This observation suggests that central nervous system pain amplification mechanisms, such as diminished conditioned pain modulation (CPM), may play a role in enhancing pain perception among some RA patients.  We examined CPM, pressure pain threshold and pressure pain tolerance among RA patients compared to controls.

Methods: Fifty-eight female RA patients and 54 age-matched controls without chronic pain underwent quantitative sensory testing to assess CPM, pressure pain threshold and pressure pain tolerance.  We induced CPM using a cold water bath, and we assessed pain threshold (when patients first felt pain) and tolerance (when pain was too much to bear) with an algometer.  Associations between RA and quantitative sensory testing measures were analyzed using linear regression models.  Sleep problems, mental health and inflammation were assessed as mediators of the relationship between RA and quantitative sensory testing measures, according to the Baron and Kenny criteria (J Pers Soc Psychol 1986).

Results:   Median CPM levels were 0.5 kg/cm² (interquartile range (IQR) -0.1, 1.6) among RA patients compared to 1.5 kg/cm² (IQR -0.1, 2.5) among controls (P = 0.04).  Relative to controls, RA patients had lower pain threshold (P = 0.03) and tolerance (P ≤ 0.004) at the wrists and knees.  Spearman’s correlations between clinical pain scores and quantitative sensory testing measures of pain varied from -0.08 for CPM to -0.31 for wrist tolerance.  Compared to controls, RA patients had greater problems with sleep, catastrophizing, depression and anxiety (P < 0.0001).  Mediation analyses showed significant associations between: 1) RA and CPM (Baron and Kenny criterion #1), 2) RA and sleep problems (Baron and Kenny criterion #2) and 3) sleep problems and CPM, adjusted for RA (Baron and Kenny criterion #3) (Figure 1).  Catastrophizing, depression and anxiety did not mediate the association between RA and CPM.

Conclusion:   RA patients have impaired CPM relative to pain-free controls.  Sleep problems may contribute to low CPM levels.  Future studies are needed to determine whether interventions to improve sleep may improve pain in RA.

Figure 1.  A. Unadjusted association between RA and conditioned pain modulation.  B.  Mediation analyses for the role of sleep problems in the association between RA and conditioned pain modulation. The change in β between the unadjusted analyses and the analyses adjusted for sleep problems indicates potential mediation, which is supported by the Baron and Kenny criteria: 1) the significant unadjusted association between RA and conditioned pain modulation, 2) the significant association between RA and sleep problems and 3) the significant association between sleep problems and conditioned pain modulation, adjusted for RA.