Although pain in rheumatoid arthritis (RA) is frequently thought to be inflammatory in nature, the association between measures of inflammation and pain intensity is low. This observation is likely due to the multifactorial nature of pain. In addition to pain from joint inflammation, RA patients may also have pain due to structural damage or central etiologies, such as aberrancies in the central nervous system (CNS) pain regulatory pathways. These CNS pathways include mechanisms that facilitate pain, as well as mechanisms that inhibit pain. Other factors, such as sleep disturbances, depression, anxiety, and catastrophizing, may also impact the perception of pain in RA patients. Since pain is frequently used as a proxy for inflammation in the assessment of RA disease activity, it is important that patients and physicians recognize that not all pain is inflammatory, and alternative management strategies, other than escalating disease-modifying antirheumatic drug treatment, may need to be considered.

High pain sensitization is associated with elevations in disease activity measures. Longitudinal studies are underway to elucidate the cause-effect relationships between pain sensitization and inflammatory disease activity in RA.

These data provide support for the utility of PROMIS measures for the assessment of physical and mental health in individuals with active RA. All PROMIS measures improved significantly after DMARD initiation, with the magnitudes of association between changes in PROMIS measures and changes in CDAI in the low to moderate range. This article is protected by copyright. All rights reserved.

Objective. Pain is a significant burden for patients with rheumatoid arthritis (RA) despite advancements in treatment. We undertook this study to examine the independent contribution of pain centralization to the pain experience of patients with active RA.Methods. A total of 263 RA patients with active disease underwent quantitative sensory testing (QST), including assessment of extraarticular pressure pain thresholds (PPTs), temporal summation (TS), and conditioned pain modulation (CPM). The pain experience was assessed by a pain intensity numeric rating scale and the Patient-Reported Outcomes Measurement Information System pain interference computerized adaptive test. We examined associations between QST measures and pain intensity and pain interference. Multiple linear regression models were adjusted for demographic and clinical variables, including swollen joint count and C-reactive protein level.Results. Patients with the lowest PPTs (most central dysregulation) reported higher pain intensity than patients with the highest PPTs (adjusted mean difference 1.02 [95% confidence interval (95% CI) 0.37, 1.67]). Patients with the highest TS (most central dysregulation) had higher pain intensity than those with the lowest TS (adjusted mean difference 1.19 [95% CI 0.54, 1.84]). CPM was not associated with differences in pain intensity. PPT and TS were not associated with pain interference. Patients with the lowest CPM (most centrally dysregulated) had lower pain interference than patients with the highest CPM (adjusted mean difference -2.35 [95% CI -4.25, -0.44]). Conclusion.Pain centralization, manifested by low PPTs and high TS, was associated with more intense pain. Clinicians should consider pain centralization as a contributor to pain intensity, independent of inflammation.

Objective Clinical trials have shown that serotonin norepinephrine reuptake inhibitors, such as milnacipran, decrease pain in non-inflammatory pain conditions like fibromyalgia and osteoarthritis. We examined the effect of milnacipran on self-reported pain intensity and experimental pain sensitivity among rheumatoid arthritis (RA) patients with widespread pain and stable RA disease activity. Methods In this double-blind, crossover study, RA patients with widespread pain, on a stable treatment regimen, were randomized (via a random number generator) to receive milnacipran 50 mg twice daily or placebo for 6 weeks, followed by a 3-week washout and crossed over to the other arm for the remaining 6 weeks. The primary outcome was change in average pain intensity, assessed by the Brief Pain Inventory short form. The sample size was calculated to detect a 30% improvement in pain with power = 0.80 and alpha = 0.05. Results Of the 43 randomized subjects, 41 received study drug, and 32 completed the 15-week study per protocol. On a 0–10 scale, average pain intensity decreased by 0.39 (95% CI −1.27, 0.49; P = 0.37) more points during 6 weeks of milnacipran treatment compared to placebo. In the subgroup of subjects with swollen joint count ≤ 1, average pain intensity decreased by 1.14 (95% CI −2.26, −0.01; P= 0.04) more points during 6 weeks of milnacipran compared to placebo. Common adverse events included nausea (26.8%) and loss of appetite (9.7%). Conclusion Compared to placebo, milnacipran did not improve overall, self-reported pain intensity among subjects with widespread pain taking stable RA medications. Trial registration: ClinicalTrials.gov NCT01207453