Objective: Many patients with rheumatoid arthritis (RA) report pain despite excellent control of inflammation with immunotherapies.
This disconnect between improvements in inflammation and improvements in pain suggests a likely contribution of pain mechanisms in addition to and distinct from peripheral inflammation. Central sensitization—a consequence of dysfunctional central nervous system (CNS) pain processing, which defines the primary chronic pain syndrome of fibromyalgia (FM)—may represent one such mechanism. This possibility is supported by clinical epidemiologic research that has found evidence of coexisting FM in 13–25% of RA patients (compared with a prevalence of 1–5% in the general population). An additional 7–15% of RA patients have hallmark features of FM (which include somatic symptoms, such as fatigue, as well as chronic pain) without meeting the ACR 1990 classification criteria. Wolfe and colleagues derived a continuous scale from the ACR FM survey criteria and found that it predicted pain and disability in RA even among patients who did not fully satisfy the FM criteria. The term fibromyalgianess (FMness) was subsequently introduced to reflect this wide phenotypic range.
The authors undertook this study to test the hypothesis that RA patients with the highest 2011 ACR FM survey criteria scores—a continuous measure of the degree of FMness—would demonstrate functional connectivity abnormalities similar to those in FM.
Methods: RA patients underwent an 11-minute functional connectivity magnetic resonance imaging (MRI) brain scan and a clinical evaluation which included a measure of FMness. Brain networks were isolated from functional connectivity MRI data. Individual patient network-to-whole brain connectivity analyses were then conducted, followed by group-level regression, which correlated the connectivity of each network with FMness.
Results: A total of 54 patients participated (mean age 54.9 years, 75.9% women, mean FMness score 13.2 [range 1–29]). From the whole brain analyses, a single significant positive correlation between DMN connectivity to the left mid/posterior insula and FMness (r=0.58, FWE-corrected P=0.001) was demonstrated.
Conclusion: RA patients who have increased levels of FMness appear to share neurobiologic features consistently observed in FM patients. This study is the first to provide neuroimaging evidence that RA is a mixed pain state, with many patients’ symptoms being related to the central nervous system rather than to classic inflammatory mechanisms.
Excerpted and adapted from:
Basu N, Kaplan CM, Ichesco E, et al. Neurobiologic features of fibromyalgia are also present among rheumatoid arthritis patients. Arthritis Rheumatol. 2018 Jul;70(7):1000–1007.
