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Dynamic pain connectome functional connectivity and oscillations reflect multiple sclerosis pain

Bosma, Rachael L.a; Kim, Junseok A.a,b; Cheng, Joshua C.a,b; Rogachov, Antona,b; Hemington, Kasey S.a,b; Osborne, Natalie R.a,b; Oh, Jiwonc; Davis, Karen D.a,b,d,*

doi: 10.1097/j.pain.0000000000001332
Research Paper
Global Year 2018

Pain is a prevalent and debilitating symptom of multiple sclerosis (MS); yet, the mechanisms underlying this pain are unknown. Previous studies have found that the functional relationships between the salience network (SN), specifically the right temporoparietal junction a SN node, and other components of the dynamic pain connectome (default mode network [DMN], ascending and descending pathways) are abnormal in many chronic pain conditions. Here, we use resting-state functional magnetic resonance imaging and measures of static and dynamic functional connectivity (sFC and dFC), and regional BOLD variability to test the hypothesis that patients with MS have abnormal DMN-SN cross-network sFC, dFC abnormalities in SN-ascending and SN-descending pathways, and disrupted BOLD variability in the dynamic pain connectome that relates to pain inference and neuropathic pain (NP). Thirty-one patients with MS and 31 controls completed questionnaires to characterize pain and pain interference, and underwent a resting-state functional magnetic resonance imaging scan from which measures of sFC, dFC, and BOLD variability were compared. We found that (1) ∼50% of our patients had NP features, (2) abnormalities in SN-DMN sFC were driven by the mixed-neuropathic subgroup, (3) in patients with mixed NP, dFC measures showed that there was a striking change in how the SN was engaged with the ascending nociceptive pathway and descending modulation pathway, (4) BOLD variability was increased in the DMN, and (5) the degrees of sFC and BOLD variability abnormalities were related to pain interference. We propose that abnormal SN-DMN cross-network FC and temporal dynamics within and between regions of the dynamic pain connectome reflect MS pain features.

The brain networks related to salience and pain was disrupted in patients with multiple sclerosis pain, and related to pain interference and neuropathic pain features.

aDivision of Brain, Imaging, and Behaviour—Systems Neuroscience, Krembil Brain Institute, Krembil Research Institute, Toronto Western Hospital, University Health Network, Toronto, ON, Canada

bInstitute of Medical Science, University of Toronto, Toronto, ON, Canada

cKeenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON, Canada

dDepartment of Surgery, University of Toronto, Toronto, ON, Canada

Corresponding author. Address: Krembil Research Institute, Toronto Western Hospital, 399 Bathurst St, Room MP12-306, Toronto, ON M5T 2S8, Canada. Tel.: (416) 603-5662. E-mail address: (K.D. Davis).

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (

Received February 10, 2018

Received in revised form June 15, 2018

Accepted June 26, 2018

© 2018 International Association for the Study of Pain
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