Influence of Morphine and Naloxone on Pain Modulation in Rheumatoid Arthritis, Chronic Fatigue Syndrome/Fibromyalgia, and Controls: A Double-Blind, Randomized, Placebo-Controlled, Cross-Over Study

Pain is a key component of most rheumatologic diseases. In fibromyalgia, the importance of central nervous system pain mechanisms (for example, loss of descending analgesic activity and central sensitization) is well documented. A few studies have also noted alterations in central pain processing in osteoarthritis, and some data, including the observation of widespread pain sensitivity, suggest that central pain-processing defects may alter the pain response in rheumatoid arthritis patients. When central pain is identified, different classes of analgesics (for example, serotonin-norepinephrine reuptake inhibitors, α2δ ligands) may be more effective than drugs that treat peripheral or nociceptive pain (for example, nonsteroidal anti-inflammatory drugs and opioids).

In order to assess the function of endogenous mechanisms modulating somatosensory input in fibromyalgia (FM), the effect of vibratory stimulation (VS) and heterotopic noxious conditioning stimulation (HNCS) on perception of various somatosensory modalities was assessed. Ten female FM patients and 10 healthy, age-matched, females participated. VS (100 Hz) was applied to the left forearm for 45 min and quantitative sensory testing (QST) was performed within the vibrated area and in the right thigh before, during and 45 min following vibration. Pressure pain thresholds (PPTs) were assessed by pressure algometry. Perception thresholds to non-painful cold (CT) and warmth (WT), heat pain thresholds (HPTs), cold pain thresholds (CPTs) and stimulus-response curves of pain intensity as a function of graded nociceptive heat stimulation were assessed using a Peltier element based thermal stimulator. The effects of HNCS were tested using the upper extremity submaximal effort tourniquet test. Subjects rated tourniquet induced pain intensity on a visual analogue scale (VAS). QST was performed in the right thigh before, during and 60 min following the tourniquet. FM patients did not differ from controls in the response to VS. There was a local increase of PPTs during vibration (P < 0.001) and of WTs following vibration (P < 0.001). HPTs increased in the forearm and in the thigh (P < 0.009) during vibration. CTs and sensitivity to suprathreshold heat pain were not influenced by VS. The intensity of pain induced by the tourniquet did not differ between groups. PPTs increased during the tourniquet in controls (P < 0.001) but not in FM patients (difference between groups P < 0.001). Decreased sensitivity to non-painful cold (P < 0.001) and non-painful warmth (P < 0.001) was seen during and following (P < 0.001; P < 0.05, respectively) the tourniquet in both groups alike. HPTs and perception of suprathreshold heat pain remained unaffected in both groups. In conclusion, FM patients did not differ from healthy controls in their response to vibration, but no modulation of pressure pain was induced by HNCS, as opposed to controls, suggesting a dysfunction in systems subserving 'diffuse noxious inhibitory controls' (DNIC).

Patients and physicians often differ in their perceptions of rheumatoid arthritis (RA) disease activity, as quantified by the patient's global assessment (PGA) and by the evaluator's global assessment (EGA). The purpose of this study was to explore the extent and reasons for this discordance. We identified variance components for the PGA and EGA in RA patients who were starting therapy with methotrexate in an academic outpatient setting. We analyzed predictors of the observed discrepancy in these measures (calculated as the PGA minus the EGA) and in their changes (calculated as the PGA(change) minus the EGA(change) ). We identified 646 RA patients, and among them, 77.4% of the variability in the PGA and 66.7% of the variability in the EGA were explainable. The main determinants for the PGA were pain (75.6%), function (1.3%, by Health Assessment Questionnaire), and number of swollen joints (0.5%); those for the EGA were the number of swollen joints (60.9%), pain (4.5%), function (0.6%), C-reactive protein (0.4%), and the number of tender joints (0.3%). Increased pain led to a discrepancy toward worse patient perception, while increased numbers of swollen joints led to a discrepancy toward worse evaluator perception, both explaining 65% of the discordance between the PGA and the EGA. Likewise, changes in pain scores and numbers of swollen joints proved to be the main determinants for discrepant perceptions of changes in RA disease activity, explaining 34.6% and 12.5% of the discordance, respectively. The most significant determinants for the cross-sectional and longitudinal discrepancy between the PGA and the EGA are pain and joint swelling, respectively. Understanding the reasons for a discordant view of disease activity will help to facilitate the sharing of decision-making in the management of RA. Copyright © 2012 by the American College of Rheumatology.