Increases in functional connectivity between pro-nociceptive brain areas may correlate with higher levels of peripheral inflammation in individuals with rheumatoid arthritis (RA) and comorbid fibromyalgia (FM), according to a study published in Arthritis & Rheumatology. The mechanisms involved in the development of FM and comorbid RA are thought to involve central sensitization.

In this study initially designed to examine the neural correlates of fatigue in RA, 54 patients with RA (75.9% women) were enrolled and divided into 2 cohorts: 27 participants with (FM+) and 27 without (FM) a diagnosis of FM, with mean scores on the American College of Rheumatology FM survey of 17.89 and 8.52, respectively.

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Participants underwent functional magnetic resonance imaging (fMRI) while taking the Paced Auditory Serial Attention Test to assess cognitive function. Seed-to-whole brain connectivity analyses were conducted, with the left mid/posterior insula and left inferior parietal lobule (IPL), which have been implicated in FM symptoms and inflammation, respectively, used as seed regions.

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The erythrocyte sedimentation rate (ESR) was used as a measure of inflammation, and the association between ESR and functional connectivity was examined using multiple regression modeling, with age and sex as covariates.

Participants in both FM groups did not differ in age, sex, or ESR. In the FM+ group, fMRI revealed increased functional connectivity between the insula and the left IPL, between the left IPL and medial prefrontal cortex, between the left IPL and dorsal anterior cingulate cortex, and  between the left IPL and other cortical areas. These enhanced connectivities were found to correlate with higher ESR levels (ie, greater levels of peripheral inflammation) in individuals in the FM+ group (P <.05 family-wise error for all). In the FM group, higher ESR levels were found to be associated with lower functional connectivity between the insula and right IPL and with higher connectivity between the IPL and left superior temporal gyrus.

Significant interaction effects between ESR levels and FM scores were established in post hoc analyses across all extracted connectivity values (P <.05 for all) except the connectivity seen between the IPL and right middle frontal gyrus (P =.317).  These results indicate ,a dynamic relationship between peripheral inflammation and functional connectivity, according to changes in FM score.

Study limitations include use of a sample that may not be representative of the larger RA population, possible bias toward a centralized pain phenotype, and uncertainty regarding the relative onset of FM and RA symptoms.

“Ultimately, the great clinical value of distinguishing ‘bottom-up’ mechanisms of central sensitization is the potential to mark out [patients with RA] whose FM symptoms may improve with an enhanced peripheral immunosuppressive approach,” noted the authors.

Disclosures: This study was supported by Pfizer Inc. Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Kaplan CM, Schrepf A, Ichesco E, et al. Inflammation is associated with pro‐nociceptive brain connections in rheumatoid arthritis patients with concomitant fibromyalgia [published online August 5, 2019]. Arthritis Rheumatol. doi:10.1002/art.41069

This article originally appeared on Clinical Pain Advisor