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Cited by 27Pain Mechanisms and TreatmentsFunctional Brain Connectivity StudiesPain Management and Treatment

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Transcriptional and cellular signatures of cortical morphometric remodelling in chronic pain

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Martins, Daniel, Dipasquale, Ottavia, Veronese, Mattia, Turkheimer, Federico, Loggia, Marco L., McMahon, Stephen, Howard, Matthew A., Williams, Steven C.R.·2022·Pain
DOI 10.1097/j.pain.0000000000002480PMC PMC8940732

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Abstract

Chronic pain is a highly debilitating and difficult to treat condition, which affects the structure of the brain. Although the development of chronic pain is moderately heritable, how disease-related alterations at the microscopic genetic architecture drive macroscopic brain abnormalities is currently largely unknown. Here, we examined alterations in morphometric similarity (MS) and applied an integrative imaging transcriptomics approach to identify transcriptional and cellular correlates of these MS changes, in 3 independent small cohorts of patients with distinct chronic pain syndromes (knee osteoarthritis, low back pain, and fibromyalgia) and age-matched and sex-matched pain-free controls. We uncover a novel pattern of cortical MS remodelling involving mostly small-to-medium MS increases in the insula and limbic cortex (none of these changes survived stringent false discovery rate correction for the number of regions tested). This pattern of changes is different from that observed in patients with major depression and cuts across the boundaries of specific pain syndromes. By leveraging transcriptomic data from Allen Human Brain Atlas, we show that cortical MS remodelling in chronic pain spatially correlates with the brain-wide expression of genes related to pain and broadly involved in the glial immune response and neuronal plasticity. Our findings bridge levels to connect genes, cell classes, and biological pathways to in vivo imaging correlates of chronic pain. Although correlational, our data suggest that cortical remodelling in chronic pain might be shaped by multiple elements of the cellular architecture of the brain and identifies several pathways that could be prioritized in future genetic association or drug development studies.

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Metadata

Authors
Martins, D., Dipasquale, O., Veronese, M., Turkheimer, F., Loggia, M. L., McMahon, S., Howard, M. A., & Williams, S. C. R.
Affiliations
  • King's College London (GB)
  • Harvard University (US)
Corresponding author
Martins, Daniel
ORCID
Venue
Pain
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2021-09-23
Volume
163
Issue
6
Pages
e759-e773
ISSN
  • 0304-3959 (ISSN-L)
  • 1872-6623
DOI
10.1097/j.pain.0000000000002480
PMC
PMC8940732
OpenAlex
W3201512041
Cited by
27
References
11
Citations by year
2026: 9 · 2025: 4 · 2024: 4 · 2023: 4 · 2022: 2 · 2021: 4
FWCI
2.20
Type
journal article
Language
en
Open access
Licence
Locations
  • Pain (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Portal (King's College London) (publishedVersion, cc-by)
  • Padua Research Archive (University of Padova) (submittedVersion)
Funders
  • National Institute for Health and Care Research
  • National Institutes of Health (1r01ns094306-01a1)
  • Medical Research Council (MR/J005142/1, MR/N026969/1)
  • National Institute on Drug Abuse (R01DA047088)
  • National Institute of Neurological Disorders and Stroke (R01‐NS‐094306, R01NS095937)
Topics
  • Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
  • Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
Keywords
chronic pain, cortical morphometry, insula, limbic cortex, knee osteoarthritis, low back pain, fibromyalgia, neuroplasticity, Allen Human Brain Atlas, gene expression, brain structure
MeSH terms
Brain, Brain Mapping, Fibromyalgia, Humans, Magnetic Resonance Imaging, Syndrome, Chronic Pain

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