{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T18:15:13Z","timestamp":1775585713678,"version":"3.50.1"},"reference-count":27,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T00:00:00Z","timestamp":1747094400000},"content-version":"vor","delay-in-days":101,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100031682","name":"Indiana University Indianapolis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100031682","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006710","name":"Wayne State University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5R00AT010012"],"award-info":[{"award-number":["5R00AT010012"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000853","name":"University of Glasgow","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000853","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007886","name":"Dana-Farber Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007886","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006733","name":"Indiana University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006733","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010506","name":"Indiana University Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010506","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","jpain.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pain"],"published-print":{"date-parts":[[2025,2]]},"DOI":"10.1016\/j.jpain.2024.104743","type":"journal-article","created":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T09:24:11Z","timestamp":1732785851000},"page":"104743","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":3,"special_numbering":"C","title":["Elevated posterior insula glutamate in patients with sickle cell disease"],"prefix":"10.1016","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5748-0414","authenticated-orcid":false,"given":"Xiaopeng","family":"Zhou","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Ichesco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew Q.","family":"Pucka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8312-6608","authenticated-orcid":false,"given":"Ziyue","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew RW","family":"O\u2019Brien","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven E.","family":"Harte","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard E.","family":"Harris","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4411-6366","authenticated-orcid":false,"given":"Ying","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"issue":"11","key":"10.1016\/j.jpain.2024.104743_bib1","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1016\/j.jpain.2015.07.005","article-title":"Frequency of hospitalizations for pain and association with altered brain network connectivity in sickle cell disease","volume":"16","author":"Darbari","year":"2015","journal-title":"J Pain"},{"issue":"1","key":"10.1016\/j.jpain.2024.104743_bib2","doi-asserted-by":"crossref","first-page":"7315","DOI":"10.1038\/s41598-024-57473-5","article-title":"Brain network hypersensitivity underlies pain crises in sickle cell disease","volume":"14","author":"Joo","year":"2024","journal-title":"Sci Rep"},{"issue":"6","key":"10.1016\/j.jpain.2024.104743_bib3","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1097\/ALN.0000000000000017","article-title":"Pregabalin rectifies aberrant brain chemistry, connectivity, and functional response in chronic pain patients","volume":"119","author":"Harris","year":"2013","journal-title":"Anesthesiology"},{"issue":"8","key":"10.1016\/j.jpain.2024.104743_bib4","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1016\/j.jpain.2014.04.007","article-title":"Altered resting state connectivity of the insular cortex in individuals with fibromyalgia","volume":"15","author":"Ichesco","year":"2014","journal-title":"J Pain"},{"key":"10.1016\/j.jpain.2024.104743_bib5","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.nicl.2014.09.007","article-title":"Resting state connectivity correlates with drug and placebo response in fibromyalgia patients","volume":"6","author":"Schmidt-Wilcke","year":"2014","journal-title":"Neuroimage Clin"},{"issue":"1","key":"10.1016\/j.jpain.2024.104743_bib6","doi-asserted-by":"crossref","first-page":"S109","DOI":"10.1016\/j.pain.2007.05.010","article-title":"Striatal grey matter increase in patients suffering from fibromyalgia--a voxel-based morphometry study","volume":"132","author":"Schmidt-Wilcke","year":"2007","journal-title":"Pain"},{"key":"10.1016\/j.jpain.2024.104743_bib7","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.trsl.2021.08.004","article-title":"Alteration of grey matter volume is associated with pain and quality of life in children with sickle cell disease","volume":"240","author":"Wang","year":"2022","journal-title":"Transl Res"},{"issue":"23","key":"10.1016\/j.jpain.2024.104743_bib8","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.1182\/bloodadvances.2017006940","article-title":"Depression, quality of life, and medical resource utilization in sickle cell disease","volume":"1","author":"Adam","year":"2017","journal-title":"Blood Adv"},{"issue":"1","key":"10.1016\/j.jpain.2024.104743_bib9","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1177\/1043454213514632","article-title":"Fatigue in adolescents and young adults with sickle cell disease: biological and behavioral correlates and health-related quality of life","volume":"31","author":"Ameringer","year":"2014","journal-title":"J Pediatr Oncol Nurs"},{"issue":"5","key":"10.1016\/j.jpain.2024.104743_bib10","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1016\/j.jpain.2016.01.475","article-title":"An evaluation of central sensitization in patients with sickle cell disease","volume":"17","author":"Campbell","year":"2016","journal-title":"J Pain"},{"issue":"23","key":"10.1016\/j.jpain.2024.104743_bib11","doi-asserted-by":"crossref","first-page":"4593","DOI":"10.1182\/blood.V126.23.4593.4593","article-title":"Evaluating causes of back pain in patients with sickle cell disease","volume":"126","author":"Whitfield","year":"2015","journal-title":"Blood"},{"issue":"3","key":"10.1016\/j.jpain.2024.104743_bib12","first-page":"598","article-title":"Clues to pathogenesis of fibromyalgia in patients with sickle cell disease","volume":"31","author":"Schlesinger","year":"2004","journal-title":"J Rheumatol"},{"issue":"10","key":"10.1016\/j.jpain.2024.104743_bib13","doi-asserted-by":"crossref","first-page":"3146","DOI":"10.1002\/art.24849","article-title":"Elevated insular glutamate in fibromyalgia is associated with experimental pain","volume":"60","author":"Harris","year":"2009","journal-title":"Arthritis Rheum"},{"issue":"3","key":"10.1016\/j.jpain.2024.104743_bib14","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1002\/art.23223","article-title":"Dynamic levels of glutamate within the insula are associated with improvements in multiple pain domains in fibromyalgia","volume":"58","author":"Harris","year":"2008","journal-title":"Arthritis Rheum"},{"issue":"2","key":"10.1016\/j.jpain.2024.104743_bib15","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1002\/art.33339","article-title":"Reduced insular gamma-aminobutyric acid in fibromyalgia","volume":"64","author":"Foerster","year":"2012","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.jpain.2024.104743_bib16","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/j.nicl.2017.11.014","article-title":"Relationships between brain metabolite levels, functional connectivity, and negative mood in urologic chronic pelvic pain syndrome patients compared to controls: a MAPP research network study","volume":"17","author":"Harper","year":"2018","journal-title":"Neuroimage Clin"},{"issue":"2","key":"10.1016\/j.jpain.2024.104743_bib17","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1016\/j.neuroimage.2010.09.039","article-title":"1H-MR spectroscopic detection of metabolic changes in pain processing brain regions in the presence of non-specific chronic low back pain","volume":"54","author":"Gussew","year":"2011","journal-title":"Neuroimage"},{"issue":"6","key":"10.1016\/j.jpain.2024.104743_bib18","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1002\/(SICI)1099-1492(199810)11:6<266::AID-NBM530>3.0.CO;2-J","article-title":"Simultaneous in vivo spectral editing and water suppression","volume":"11","author":"Mescher","year":"1998","journal-title":"NMR Biomed"},{"issue":"6","key":"10.1016\/j.jpain.2024.104743_bib19","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1002\/mrm.1910300604","article-title":"Estimation of metabolite concentrations from localized in vivo proton NMR spectra","volume":"30","author":"Provencher","year":"1993","journal-title":"Magn Reson Med"},{"issue":"6","key":"10.1016\/j.jpain.2024.104743_bib20","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1002\/jmri.24478","article-title":"Gannet: a batch-processing tool for the quantitative analysis of gamma-aminobutyric acid-edited MR spectroscopy spectra","volume":"40","author":"Edden","year":"2014","journal-title":"J Magn Reson Imaging"},{"issue":"3","key":"10.1016\/j.jpain.2024.104743_bib21","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/j.neuroimage.2005.02.018","article-title":"Unified segmentation","volume":"26","author":"Ashburner","year":"2005","journal-title":"Neuroimage"},{"issue":"1","key":"10.1016\/j.jpain.2024.104743_bib22","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-020-76263-3","article-title":"Metabolite activity in the anterior cingulate cortex during a painful stimulus using functional MRS","volume":"10","author":"Archibald","year":"2020","journal-title":"Sci Rep"},{"key":"10.1016\/j.jpain.2024.104743_bib23","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/j.nicl.2018.09.008","article-title":"Neurotransmitter alterations in the anterior cingulate cortex in Crohn's disease patients with abdominal pain: a preliminary MR spectroscopy study","volume":"20","author":"Lv","year":"2018","journal-title":"Neuroimage Clin"},{"issue":"3","key":"10.1016\/j.jpain.2024.104743_bib24","article-title":"Brain gamma-aminobutyric acid, but not glutamine and glutamate levels are lower in older adults with chronic musculoskeletal pain: considerations by sex and brain location","volume":"6","author":"Cruz-Almeida","year":"2021","journal-title":"Pain Rep."},{"key":"10.1016\/j.jpain.2024.104743_bib25","doi-asserted-by":"crossref","DOI":"10.1016\/j.neuroimage.2020.116532","article-title":"Brain GABA and glutamate levels across pain conditions: a systematic literature review and meta-analysis of 1H-MRS studies using the MRS-Q quality assessment tool","volume":"210","author":"Peek","year":"2020","journal-title":"Neuroimage"},{"issue":"1-2","key":"10.1016\/j.jpain.2024.104743_bib26","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.pain.2008.12.008","article-title":"Painful tonic heat stimulation induces GABA accumulation in the prefrontal cortex in man","volume":"142","author":"Kupers","year":"2009","journal-title":"Pain"},{"issue":"7","key":"10.1016\/j.jpain.2024.104743_bib27","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1002\/art.41620","article-title":"Greater somatosensory afference with acupuncture increases primary somatosensory connectivity and alleviates fibromyalgia pain via insular gamma-aminobutyric acid: a randomized neuroimaging trial","volume":"73","author":"Mawla","year":"2021","journal-title":"Arthritis Rheumatol"}],"container-title":["The Journal of Pain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1526590024007211?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1526590024007211?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T12:20:21Z","timestamp":1770639621000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1526590024007211"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2]]},"references-count":27,"alternative-id":["S1526590024007211"],"URL":"https:\/\/doi.org\/10.1016\/j.jpain.2024.104743","relation":{},"ISSN":["1526-5900"],"issn-type":[{"value":"1526-5900","type":"print"}],"subject":[],"published":{"date-parts":[[2025,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Elevated posterior insula glutamate in patients with sickle cell disease","name":"articletitle","label":"Article Title"},{"value":"The Journal of Pain","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jpain.2024.104743","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 The Author(s). Published by Elsevier Inc. on behalf of United States Association for the Study of Pain, Inc","name":"copyright","label":"Copyright"}],"article-number":"104743"}}