{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:20:41Z","timestamp":1787026841407,"version":"build-2736575974"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T00:00:00Z","timestamp":1700092800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["U01 EY034686"],"award-info":[{"award-number":["U01 EY034686"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["U24EY035102"],"award-info":[{"award-number":["U24EY035102"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R33EY032468"],"award-info":[{"award-number":["R33EY032468"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The factors that mediate the expression of ocular pain and the mechanisms that promote chronic ocular pain symptoms are poorly understood. Central nervous system involvement has been postulated based on observations of pain out of proportion to nociceptive stimuli in some individuals. This investigation focused on understanding functional connectivity between brain regions implicated in chronic pain in persons reporting ocular pain symptoms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We recruited a total of 53 persons divided into two cohorts: persons who reported no ocular pain, and persons who reported chronic ocular pain, irrespective of ocular surface findings. We performed a resting state fMRI investigation that was focused on subcortical brain structures including the trigeminal nucleus and performed a brief battery of ophthalmological examinations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Persons in the pain cohort reported higher levels of pain symptoms relating to neuropathic pain and ocular surface disease, as well as more abnormal tear metrics (stability and tear production). Functional connectivity analysis between groups evinced multiple connections exemplifying both increases and decreases in connectivity including regions such as the trigeminal nucleus, amygdala, and sub-regions of the thalamus. Exploratory analysis of the pain cohort integrating clinical and brain function metrics highlighted subpopulations that showed unique phenotypes providing insight into pain mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Study findings support centralized involvement in those reporting ocular-based pain and allude to mechanisms through which pain treatment services may be directed in future research.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2023.1265082","type":"journal-article","created":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T13:16:23Z","timestamp":1700140583000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Disentangling the neurological basis of chronic ocular pain using clinical, self-report, and brain imaging data: use of K-means clustering to explore patient phenotypes"],"prefix":"10.3389","volume":"14","author":[{"given":"Scott","family":"Holmes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Reyes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaxon J.","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anat","family":"Galor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradip M.","family":"Pattany","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth R.","family":"Felix","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric A.","family":"Moulton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,11,16]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1186\/s12348-016-0114-z","article-title":"Prevalence of ocular surface disease symptoms and risk factors in group of university students in Monterrey, Mexico","volume":"6","author":"Garza-Le\u00f3n","year":"2016","journal-title":"J Ophthalmic Inflamm Infect"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ajo.2011.05.033","article-title":"Ocular surface disease and quality of life in patients with Glaucoma","volume":"153","author":"Skalicky","year":"2012","journal-title":"Am J Ophthalmol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"75","DOI":"10.4274\/tjo.galenos.2019.29000","article-title":"Correlation of ocular surface disease and quality of life in Indian Glaucoma patients: BAC-preserved versus BAC-free Travoprost","volume":"50","author":"Kumar","year":"2020","journal-title":"Turk J Ophthalmol"},{"key":"ref4","volume-title":"Ocular Neuropathic Pain","author":"Moshirfar","year":"2023"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1016\/j.ophtha.2008.10.011","article-title":"Bevacizumab for corneal neovascularization","volume":"116","author":"Jacobs","year":"2009","journal-title":"Ophthalmology"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1001\/jamaneurol.2018.0602","article-title":"Controversie and future directions of ocular biomarkers in alzheimer disease","volume":"75","author":"Ong","year":"2018","journal-title":"JAMA Neurol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1872","DOI":"10.1177\/11206721211060963","article-title":"Dry eye disease and psychiatric disorders: a systematic review and meta-analysis","volume":"32","author":"Basilious","year":"2022","journal-title":"Eur J Ophthalmol"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1001\/jamaophthalmol.2022.0146","article-title":"How depression might relate to dry eye disease","volume":"140","author":"Galor","year":"2022","journal-title":"JAMA Ophthamol"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1136\/bjophthalmol-2015-308214","article-title":"Patients with more severe symptoms of neuropathic ocular pain report more frequent and severe chronic overlapping pain conditions and psychiatric disease","volume":"101","author":"Crane","year":"2017","journal-title":"Br J Ophthalmol"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.jtos.2012.01.002","article-title":"The corneal pain system. 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