Pain in Active Rheumatoid Arthritis May Be Associated With Pain Centralization

rheumatoid arthritis
rheumatoid arthritis
A significant association between pain intensity and pain centralization was established in patients with active rheumatoid arthritis.

A significant association between pain intensity and pain centralization was established in patients with active rheumatoid arthritis (RA), according to a study published in Arthritis Care & Research.

Despite therapeutic advances, pain remains a challenge for patients with RA. Once believed to be the result of peripheral nociception secondary to inflammation, pain in RA is now also thought to result from centralization of the phenomenon, although the mechanisms underlying these processes are not clearly understood. A better understanding of the role pain centralization plays in RA would allow clinicians to distinguish inflammatory nociceptive pain from centralized pain, and thus enable them to prescribe more appropriate treatments for patients.

For the Central Pain in RA (CPIRA) study — a multicenter observational study conducted between January 2014 and June 2017 — 263 participants (mean age, 54.7 years; 81.8% women; 74.9% white; 73.0% seropositive; mean disease duration, 9.8 years; mean C reactive protein level [CRP], 7.9 mg/L; mean swollen joint count [SJC], 5.1) with active RA who were initiating or changing their treatment with disease-modifying anti-rheumatic drugs were enrolled. The goal of the study was to explore the relationship between central pain mechanisms and self-reported pain experiences (ie, pain intensity and pain interference), using quantitative sensory testing (QST) that included extra-articular (at the trapezius muscle) pressure pain thresholds (PPTs), temporal summation (TS) and conditioned pain modulation (CPM).

Pain experiences were assessed using a numeric rating scale for intensity (primary outcome) and the Patient-Reported Outcomes Measurement Information System Pain Interference computerized adaptive test (secondary outcome). Associations between pain experiences and QST measures were calculated using multiple linear regression modeling adjusted for clinical and demographic variables, including CRP and SJC.

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Study participants with the lowest vs highest PPTs (ie, with the greatest central dysregulation) had higher pain intensities (adjusted mean difference, 1.02; 95% CI, 0.37-1.67; P =.002). Participants with the highest TS (ie, with the greatest central dysregulation) vs lowest TS had greater pain intensities (adjusted mean difference, 1.19; 95% CI, 0.54-1.84; P <.001). There was no correlation between CPM and differences in pain intensity.

Lower pain interference was reported by participants with the lowest CPM (greatest central dysregulation) compared with patients with the highest CPM (adjusted mean difference, −2.35; 95% CI, −4.25 to −0.44; P =.016). There was no association between interference and PPTs or TS.

Study strengths include a large sample size, multiple QST measures, adjustment for potential confounders, use of a validated QST protocol, and the inclusion of multiple centers.

Study limitations include QST heterogeneity across sites, low CPM reproducibility, and a cross-sectional design that precludes causal inferences.

“This study implicates pain centralization as a contributor to pain in patients with RA,

independent of the effects of inflammation. Clinicians should consider pain centralization as a contributor to patient-reported pain when tailoring individualized therapy for patients with RA,” concluded the study authors. They recommended that future research evaluate the optimal CPM protocol.


Yvonne C. Lee, MD, MMSc reports advisory board membership for Eli Lilly (unpaid), stock

ownership in Express Scripts, and a research grant from Pfizer. Marcy Bolster reports

educational grants from Abbvie and Pfizer, advisory board membership for Johnson and

Johnson, and investments in Gilead. Daniel J. Clauw MD has received consulting fees from

Aptinyx, Daiichi Sankyo, Intec Pharma, Eli Lilly, Pfizer, Samumed, Theravance, Tonix, and

Zynerba (less than $10,000 per single occurrence).

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Heisler AC, Song J, Dunlop DD, et al. Association of pain centralization and patient‐reported pain in active rheumatoid arthritis. Arthritis Care Res (Hoboken) [published online June 2019]. doi:10.1002/acr.23994