{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T17:37:14Z","timestamp":1788802634466,"version":"build-2803163510"},"reference-count":61,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":113,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Chronic pain is a leading contributor to all-cause morbidity and disability, encompassing numerous biopsychosocial dimensions that persistently engage complex networks of brain regions. Meta-analyses have advanced our understanding of structural brain differences in chronic pain but rely exclusively on summary statistics which may introduce heterogeneity related to completeness of reporting and differences in methodological approaches. To address these limitations, we conducted the first individual participant data (IPD) meta-analysis of brain structure alterations in chronic pain. Using traditional morphometric measures (i.e. volume, cortical thickness, and surface area) and differential-geometric shape metrics (i.e. intrinsic and extrinsic curvature), we aimed to reveal alterations in brain structure convergent across chronic pain conditions. We hypothesized that chronic pain would be associated with region-specific grey matter reductions in regions previously implicated in chronic pain (e.g. parahippocampal gyrus and insula) and explored whether curvature metrics would reveal additional structural changes. Anatomical MRI images from eight publicly available datasets spanning five conditions and 401 individuals with chronic pain (and 245 age- and sex- matched healthy controls) were analysed: (i) knee osteoarthritis, (ii) chronic low back pain, (iii) fibromyalgia, (iv) migraine, and (v) primary trigeminal neuralgia. FreeSurfer was used to parcellate T1-weighted anatomical images, and metrics for cortical and subcortical regions were extracted. Meta-analysis revealed a range of structural changes in the brain associated with chronic pain. Cortical thinning and volume loss were small and localized to the temporo-occipital regions, including bilateral volumetric reductions in the entorhinal cortex in individuals with chronic pain. Increases in intrinsic curvature were widespread, involving 49 out of 68 cortical regions. No significant alterations were detected in subcortical volumes. Intrinsic curvature and subcortical volumetric estimates had higher levels of inter-study heterogeneity compared to other metrics, reflecting potential condition and sample-specific variability. Leveraging harmonized processing across a large sample size, our novel IPD meta-analysis highlights both widespread and region-specific structural remodelling of chronic pain-related neuroanatomy.<\/jats:p>","DOI":"10.1093\/braincomms\/fcag146","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T11:49:47Z","timestamp":1776858587000},"source":"Crossref","is-referenced-by-count":2,"title":["Convergent structural brain alterations in chronic pain: a multi-metric individual participant data meta-analysis"],"prefix":"10.1093","volume":"8","author":[{"given":"Ryan W J","family":"Loke","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Pharmacology, and Therapeutics, Faculty of Medicine, University of British Columbia , Vancouver, Bc v6t 1z3 ,","place":["Canada"]},{"name":"International Collaborations on Repair Discoveries (ICORD), University of British Columbia , Vancouver, Bc v5z 1n1 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Ortiz","sequence":"additional","affiliation":[{"name":"International Collaborations on Repair Discoveries (ICORD), University of British Columbia , Vancouver, Bc v5z 1n1 ,","place":["Canada"]},{"name":"School of Biomedical Engineering, Faculty of Applied Sciences, University of British Columbia , Vancouver, Bc v6t 2b9 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia M","family":"Gustin","sequence":"additional","affiliation":[{"name":"NeuroRecovery Research Hub, School of Psychology, The University of New South Wales (UNSW) Sydney , Sydney, NSW 2052 ,","place":["Australia"]},{"name":"Centre for Pain IMPACT, Neuroscience Research Australia , Randwick, NSW 2031 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mich\u00e8le","family":"Hubli","sequence":"additional","affiliation":[{"name":"Spinal Cord Injury Center, Balgrist University Hospital, University of Zurich , Zurich 8008 ,","place":["Switzerland"]},{"name":"Neuroscience Center Zurich, ETH Zurich and University of Zurich , Zurich 8057 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clas","family":"Linnman","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Massachusetts General Brigham & Harvard Medical School , Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2216-7357","authenticated-orcid":false,"given":"Abigail","family":"Livny","sequence":"additional","affiliation":[{"name":"Clinical Brain Imaging R&D Center, Sheba Medical Center , Tel Aviv 5262000 ,","place":["Israel"]},{"name":"Sagol School of Neuroscience, Faculty of Medical and Health Sciences, Tel Aviv University , Tel Aviv 6997801 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8569-7139","authenticated-orcid":false,"given":"Yann","family":"Quid\u00e9","sequence":"additional","affiliation":[{"name":"NeuroRecovery Research Hub, School of Psychology, The University of New South Wales (UNSW) Sydney , Sydney, NSW 2052 ,","place":["Australia"]},{"name":"Centre for Pain IMPACT, Neuroscience Research Australia , Randwick, NSW 2031 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7568-0133","authenticated-orcid":false,"given":"Paulina S","family":"Scheuren","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Pharmacology, and Therapeutics, Faculty of Medicine, University of British Columbia , Vancouver, Bc v6t 1z3 ,","place":["Canada"]},{"name":"International Collaborations on Repair Discoveries (ICORD), University of British Columbia , Vancouver, Bc v5z 1n1 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John L K","family":"Kramer","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Pharmacology, and Therapeutics, Faculty of Medicine, University of British Columbia , Vancouver, Bc v6t 1z3 ,","place":["Canada"]},{"name":"International Collaborations on Repair Discoveries (ICORD), University of British Columbia , Vancouver, Bc v5z 1n1 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"issue":"2","key":"2026050811381565800_fcag146-B1","first-page":"e273","article-title":"Chronic pain: A review of its epidemiology and associated factors in population-based studies","volume":"123","author":"Mills","year":"2019","journal-title":"Br J Anaesth"},{"issue":"6","key":"2026050811381565800_fcag146-B2","first-page":"605","article-title":"The emotional brain as a predictor and amplifier of chronic pain","volume":"95","author":"Vachon-Presseau","year":"2016","journal-title":"J Dent Res"},{"issue":"13","key":"2026050811381565800_fcag146-B3","first-page":"3130","article-title":"Chronic pain: Structural and functional changes in brain structures and associated negative affective states","volume":"20","author":"Yang","year":"2019","journal-title":"Int J Mol Sci"},{"issue":"1","key":"2026050811381565800_fcag146-B4","article-title":"Altered brain structure and function correlate with disease severity and pain catastrophizing in migraine patients","volume":"1","author":"Hubbard","year":"2014","journal-title":"eNeuro"},{"issue":"12","key":"2026050811381565800_fcag146-B5","first-page":"3293","article-title":"Overlapping structural and functional brain changes in patients with long-term exposure to fibromyalgia pain","volume":"65","author":"Jensen","year":"2013","journal-title":"Arthritis Rheum"},{"issue":"7","key":"2026050811381565800_fcag146-B6","first-page":"592","article-title":"Cortical thickness alterations in chronic pain disorder: An exploratory MRI study","volume":"80","author":"Magon","year":"2018","journal-title":"Psychosom Med"},{"key":"2026050811381565800_fcag146-B7","first-page":"676","article-title":"Gray matter alterations in chronic pain: A network-oriented meta-analytic approach","volume":"4","author":"Cauda","year":"2014","journal-title":"Neuroimage Clin"},{"key":"2026050811381565800_fcag146-B8","first-page":"130","article-title":"Grey matter alterations in migraine: A systematic review and meta-analysis","volume":"14","author":"Jia","year":"2017","journal-title":"Neuroimage Clin"},{"issue":"3","key":"2026050811381565800_fcag146-B9","first-page":"330","article-title":"Gray matter abnormalities associated with fibromyalgia: A meta-analysis of voxel-based morphometric studies","volume":"46","author":"Shi","year":"2016","journal-title":"Semin Arthritis Rheum"},{"issue":"1","key":"2026050811381565800_fcag146-B10","first-page":"e10","article-title":"Structural imaging studies of patients with chronic pain: An anatomical likelihood estimate meta-analysis","volume":"164","author":"Henn","year":"2023","journal-title":"Pain"},{"issue":"7","key":"2026050811381565800_fcag146-B11","first-page":"663","article-title":"Structural brain anomalies and chronic pain: A quantitative meta-analysis of gray matter volume","volume":"14","author":"Smallwood","year":"2013","journal-title":"J Pain"},{"issue":"11","key":"2026050811381565800_fcag146-B12","first-page":"983","article-title":"Gray matter abnormalities associated with chronic back pain","volume":"33","author":"Yuan","year":"2017","journal-title":"Clin J Pain"},{"issue":"9","key":"2026050811381565800_fcag146-B13","first-page":"1224","article-title":"Quantitative meta-analysis of grey matter anomalies in neuropathic pain","volume":"19","author":"Pan","year":"2015","journal-title":"Eur J Pain"},{"issue":"2","key":"2026050811381565800_fcag146-B14","article-title":"Highlighting the benefits and disadvantages of individual participant data meta-analysis in radiology","volume":"6","author":"Costa","year":"2024","journal-title":"Radiol Imaging Cancer"},{"issue":"3","key":"2026050811381565800_fcag146-B15","first-page":"320","article-title":"Meta-analysis in medical research: Potentials and limitations","volume":"26","author":"Zwahlen","year":"2008","journal-title":"Urol Oncol."},{"issue":"1","key":"2026050811381565800_fcag146-B16","article-title":"Global disruption of degree rank order: A hallmark of chronic pain","volume":"6","author":"Mansour","year":"2016","journal-title":"Sci Rep"},{"issue":"1","key":"2026050811381565800_fcag146-B17","first-page":"129","article-title":"Chronic pain: The role of learning and brain plasticity","volume":"32","author":"Mansour","year":"2014","journal-title":"Restor Neurol Neurosci"},{"key":"2026050811381565800_fcag146-B18","article-title":"Pain-sensorimotor interactions: New perspectives and a new model","volume":"15","author":"Murray","year":"2024","journal-title":"Neurobiol Pain"},{"key":"2026050811381565800_fcag146-B19","first-page":"61","article-title":"Psychological processing in chronic pain: A neural systems approach","volume":"39","author":"Simons","year":"2014","journal-title":"Neurosci Biobehav Rev"},{"issue":"10","key":"2026050811381565800_fcag146-B20","article-title":"Brain morphological signatures for chronic pain","volume":"6","author":"Baliki","year":"2011","journal-title":"PLoS One"},{"issue":"23","key":"2026050811381565800_fcag146-B21","first-page":"1102","article-title":"An introduction to individual participant data meta-analysis","volume":"100","author":"Veroniki","year":"2023","journal-title":"Neurology"},{"key":"2026050811381565800_fcag146-B22","first-page":"475","article-title":"Increased cortical curvature reflects white matter atrophy in individual patients with early multiple sclerosis","volume":"6","author":"Deppe","year":"2014","journal-title":"Neuroimage Clin"},{"issue":"05","key":"2026050811381565800_fcag146-B23","first-page":"351","article-title":"Intrinsic curvature: A marker of millimeter-scale tangential cortico-cortical connectivity?","volume":"21","author":"Ronan","year":"2011","journal-title":"Int J Neural Syst"},{"issue":"1","key":"2026050811381565800_fcag146-B24","first-page":"255","article-title":"Mega-analysis methods in ENIGMA: The experience of the generalized anxiety disorder working group","volume":"43","author":"Zugman","year":"2022","journal-title":"Hum Brain Mapp"},{"issue":"2","key":"2026050811381565800_fcag146-B25","first-page":"1052","article-title":"General multilevel linear modeling for group analysis in FMRI","volume":"20","author":"Beckmann","year":"2003","journal-title":"Neuroimage"},{"issue":"1","key":"2026050811381565800_fcag146-B26","first-page":"1","article-title":"A general statistical analysis for fMRI data","volume":"15","author":"Worsley","year":"2002","journal-title":"Neuroimage"},{"key":"2026050811381565800_fcag146-B27","article-title":"The OpenNeuro resource for sharing of neuroscience data","volume":"10","author":"Markiewicz","year":"2021","journal-title":"Elife"},{"issue":"4","key":"2026050811381565800_fcag146-B28","first-page":"825","article-title":"Similarity of suffering: Equivalence of psychological and psychosocial factors in neuropathic and non-neuropathic orofacial pain patients","volume":"152","author":"Gustin","year":"2011","journal-title":"Pain"},{"issue":"6","key":"2026050811381565800_fcag146-B29","first-page":"615","article-title":"Neuroimaging chronic pain: What have we learned and where are we going?","volume":"9","author":"Martucci","year":"2014","journal-title":"Future Neurol"},{"key":"2026050811381565800_fcag146-B30","article-title":"Chronic pain-induced functional and structural alterations in the brain: A multi-modal meta-analysis","volume":"28","author":"Zeng","year":"2025","journal-title":"J Pain"},{"issue":"2","key":"2026050811381565800_fcag146-B31","first-page":"203","article-title":"Open Science Framework (OSF)","volume":"105","author":"Foster","year":"2017","journal-title":"J Med Libr Assoc."},{"issue":"2","key":"2026050811381565800_fcag146-B32","first-page":"774","article-title":"FreeSurfer","volume":"62","author":"Fischl","year":"2012","journal-title":"Neuroimage"},{"issue":"3","key":"2026050811381565800_fcag146-B33","first-page":"341","article-title":"Whole brain segmentation","volume":"33","author":"Fischl","year":"2002","journal-title":"Neuron"},{"issue":"5","key":"2026050811381565800_fcag146-B34","first-page":"552","article-title":"Identification of common variants associated with human hippocampal and intracranial volumes","volume":"44","author":"Stein","year":"2012","journal-title":"Nat Genet"},{"key":"2026050811381565800_fcag146-B35","doi-asserted-by":"publisher","author":"Anderson","DOI":"10.32614\/CRAN.package.esvis"},{"issue":"3","key":"2026050811381565800_fcag146-B36","first-page":"1","article-title":"Conducting meta-analyses in R with the metafor package","volume":"36","author":"Viechtbauer","year":"2010","journal-title":"J Stat Softw"},{"key":"2026050811381565800_fcag146-B37","author":"Schwarzer"},{"issue":"10","key":"2026050811381565800_fcag146-B38","article-title":"Brain connectivity predicts placebo response across chronic pain clinical trials","volume":"14","author":"T\u00e9treault","year":"2016","journal-title":"PLoS Biol"},{"issue":"18","key":"2026050811381565800_fcag146-B39","first-page":"10015","article-title":"Loss of nucleus accumbens low-frequency fluctuations is a signature of chronic pain","volume":"117","author":"Makary","year":"2020","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026050811381565800_fcag146-B40","first-page":"19","article-title":"Classification and characterisation of brain network changes in chronic back pain: A multicenter study","volume":"3","author":"Mano","year":"2018","journal-title":"Wellcome Open Res"},{"issue":"1","key":"2026050811381565800_fcag146-B41","first-page":"15486","article-title":"Functional connectivity of music-induced analgesia in fibromyalgia","volume":"9","author":"Pando-Naude","year":"2019","journal-title":"Sci Rep"},{"issue":"1","key":"2026050811381565800_fcag146-B42","first-page":"581","article-title":"A behavioral and brain imaging dataset with focus on emotion regulation of women with fibromyalgia","volume":"9","author":"Balducci","year":"2022","journal-title":"Sci Data"},{"issue":"8","key":"2026050811381565800_fcag146-B43","first-page":"1837","article-title":"Enhanced mindfulness-based stress reduction in episodic migraine: A randomized clinical trial with magnetic resonance imaging outcomes","volume":"161","author":"Seminowicz","year":"2020","journal-title":"Pain"},{"issue":"1","key":"2026050811381565800_fcag146-B44","article-title":"Hippocampal subfield abnormalities in patients with primary trigeminal neuralgia","volume":"35","author":"Filimonova","year":"2025","journal-title":"J Neuroimaging."},{"issue":"1","key":"2026050811381565800_fcag146-B45","first-page":"43","article-title":"Cortical thickness and pain sensitivity in zen meditators","volume":"10","author":"Grant","year":"2010","journal-title":"Emotion"},{"issue":"10","key":"2026050811381565800_fcag146-B46","first-page":"4380","article-title":"Entorhinal cortex","volume":"6","author":"Witter","year":"2011","journal-title":"Scholarpedia"},{"issue":"4","key":"2026050811381565800_fcag146-B47","first-page":"464","article-title":"Pain perception in relation to emotional learning","volume":"18","author":"Apkarian","year":"2008","journal-title":"Curr Opin Neurobiol"},{"issue":"12","key":"2026050811381565800_fcag146-B48","first-page":"2662","article-title":"ENIGMA-Chronic Pain: A worldwide initiative to identify brain correlates of chronic pain","volume":"165","author":"Quid\u00e9","year":"2024","journal-title":"Pain"},{"issue":"6","key":"2026050811381565800_fcag146-B49","first-page":"1398","article-title":"Beyond feeling: Chronic pain hurts the brain, disrupting the default-mode network dynamics","volume":"28","author":"Baliki","year":"2008","journal-title":"J Neurosci"},{"issue":"1","key":"2026050811381565800_fcag146-B50","first-page":"160","article-title":"Beyond the chronic pain stage: Default mode network perturbation depends on years lived with back pain","volume":"166","author":"Heukamp","year":"2025","journal-title":"Pain"},{"issue":"5","key":"2026050811381565800_fcag146-B51","article-title":"Multi-network dynamical structure of the human brain in the setting of chronic pain: A coordinate-based meta-analysis","volume":"7","author":"Dhanaraj","year":"2025","journal-title":"Brain Commun"},{"issue":"6","key":"2026050811381565800_fcag146-B52","first-page":"2064","article-title":"Cortical thickness systematically varies with curvature and depth in healthy human brains","volume":"43","author":"Demirci","year":"2022","journal-title":"Hum Brain Mapp"},{"issue":"8","key":"2026050811381565800_fcag146-B53","first-page":"692","article-title":"The lateral prefrontal cortex mediates the hyperalgesic effects of negative cognitions in chronic pain patients","volume":"16","author":"Loggia","year":"2015","journal-title":"J Pain"},{"key":"2026050811381565800_fcag146-B54","article-title":"Functional alterations in the posterior insula and cerebellum in migraine without aura: A resting-state MRI study","volume":"14","author":"Ke","year":"2020","journal-title":"Front Behav Neurosci"},{"issue":"2","key":"2026050811381565800_fcag146-B55","first-page":"110","article-title":"Aberrant resting-state functional connectivity in Complex regional pain syndrome: A network-based statistics analysis","volume":"32","author":"Hong","year":"2023","journal-title":"Exp Neurobiol"},{"issue":"1","key":"2026050811381565800_fcag146-B56","first-page":"7515","article-title":"Disrupted topological organization of brain connectome in patients with chronic low back related leg pain and clinical correlations","volume":"15","author":"Ji","year":"2025","journal-title":"Sci Rep"},{"issue":"1-2","key":"2026050811381565800_fcag146-B57","first-page":"604","article-title":"Sex-based differences in brain alterations across chronic pain conditions","volume":"95","author":"Gupta","year":"2017","journal-title":"J Neurosci Res"},{"issue":"10","key":"2026050811381565800_fcag146-B58","first-page":"836","article-title":"Effect of ibuprofen on BrainAGE: A randomized, placebo-controlled, dose-response exploratory study","volume":"3","author":"Le","year":"2018","journal-title":"Biol Psychiatry Cogn Neurosci Neuroimaging"},{"issue":"1","key":"2026050811381565800_fcag146-B59","first-page":"17","article-title":"Cuneus and fusiform cortices thickness is reduced in trigeminal neuralgia","volume":"15","author":"Parise","year":"2014","journal-title":"J Headache Pain"},{"issue":"Suppl 16","key":"2026050811381565800_fcag146-B60","article-title":"Automated FreeSurfer segmentation and visual quality control in 10,000 MRI scans from a large memory clinic cohort","volume":"19","author":"Bocancea","year":"2023","journal-title":"Alzheimers Dement"},{"issue":"4","key":"2026050811381565800_fcag146-B61","first-page":"1515","article-title":"Multisite test-retest reliability and compatibility of brain metrics derived from FreeSurfer versions 7.1, 6.0, and 5.3","volume":"44","author":"Haddad","year":"2023","journal-title":"Hum Brain Mapp"}],"container-title":["Brain Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/braincomms\/advance-article-pdf\/doi\/10.1093\/braincomms\/fcag146\/68155833\/fcag146.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/braincomms\/article-pdf\/8\/3\/fcag146\/68155833\/fcag146.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/braincomms\/article-pdf\/8\/3\/fcag146\/68155833\/fcag146.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T15:38:21Z","timestamp":1778254701000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/braincomms\/article\/doi\/10.1093\/braincomms\/fcag146\/8662069"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":61,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,5,5]]}},"URL":"https:\/\/doi.org\/10.1093\/braincomms\/fcag146","relation":{},"ISSN":["2632-1297"],"issn-type":[{"value":"2632-1297","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026]]},"published":{"date-parts":[[2026]]},"article-number":"fcag146"}}