Brief Report: Decreased intrinsic brain connectivity is associated with reduced clinical pain in fibromyalgia


  • Vitaly Napadow,

    Corresponding author
    1. Massachusetts General Hospital, Charlestown, and Logan College of Chiropractic, Chesterfield, Missouri
    • Martinos Center for Biomedical Imaging, 149 13th Street #2301, Charlestown, MA 02129
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  • Jieun Kim,

    1. Massachusetts General Hospital, Charlestown
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  • Daniel J. Clauw,

    1. University of Michigan, Ann Arbor
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    • Dr. Clauw has received consulting fees, speaking fees, and/or honoraria from Cypress Biosciences, Eli Lilly, Forest Laboratories, Jazz Pharmaceuticals, Merck, UCB, Pierre Fabre Pharmaceuticals, and Pfizer (more than $10,000 each) and has received grant funding from Merck and Forest Laboratories.

  • Richard E. Harris

    1. University of Michigan, Ann Arbor
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    • Dr. Harris has received consulting fees from Pfizer (less than $10,000) and has received grant funding from Pfizer.

  • This content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Complementary and Alternative Medicine, the Department of the Army, or the Dana Foundation.



A major impediment to the development of novel treatment strategies for fibromyalgia (FM) is the lack of an objective marker that reflects spontaneously reported clinical pain in patients with FM. Studies of resting-state intrinsic brain connectivity in FM have demonstrated increased insular connectivity to the default mode network (DMN), a network whose activity is increased during nontask states. Moreover, increased insular connectivity to the DMN was associated with increased spontaneous pain levels. However, as these analyses were cross-sectional in nature, they provided no insight into dynamic changes in connectivity or their relationship to variations in self-reported clinical pain. The purpose of this study was to evaluate longitudinal changes in the intrinsic brain connectivity of FM patients treated with nonpharmacologic interventions known to modulate pain levels in this patient population, and to test the hypothesis that the reduction of DMN–insula connectivity following therapy would correlate with diminished pain.


Seventeen FM patients underwent resting-state functional magnetic resonance imaging at baseline and following 4 weeks of a nonpharmacologic intervention to diminish pain. Intrinsic DMN connectivity was evaluated using probabilistic independent components analysis. Longitudinal changes in intrinsic DMN connectivity were evaluated by paired analysis, and correlations between longitudinal changes in clinical pain and changes in intrinsic DMN connectivity were investigated by multiple linear regression analysis. Changes in clinical pain were assessed with the short form of the McGill Pain Questionnaire (SF-MPQ).


Clinical pain as assessed using the sensory scale of the SF-MPQ was reduced following therapy (P = 0.02). Intrinsic DMN connectivity to the insula was reduced, and this reduction correlated with reductions in pain (corrected P < 0.05).


Our findings suggest that intrinsic brain connectivity can be used as a candidate objective marker that reflects changes in spontaneous chronic pain within individual FM patients. We propose that intrinsic connectivity measures could potentially be used in either research or clinical settings as a complementary, more objective outcome measure for use in FM.