{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T12:38:43Z","timestamp":1791376723906,"version":"4.3.2"},"reference-count":75,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,12,29]],"date-time":"2023-12-29T00:00:00Z","timestamp":1703808000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pain"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Trigeminal neuralgia (TN) is a severe facial pain condition often associated with a neurovascular conflict. However, neuroinflammation has also been implicated in TN, as it frequently co\u2010occurs with multiple sclerosis (MS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analysed protein expression levels of TN patients compared to MS patients and controls. Proximity Extension Assay technology was used to analyse the levels of 92 proteins with the Multiplex Neuro\u2010Exploratory panel provided by SciLifeLab, Uppsala, Sweden. Serum and CSF samples were collected from TN patients before (<jats:italic>n<\/jats:italic>\u2009=\u200933 and <jats:italic>n<\/jats:italic>\u2009=\u200927, respectively) and after (<jats:italic>n<\/jats:italic>\u2009=\u200928 and <jats:italic>n<\/jats:italic>\u2009=\u20098, respectively) microvascular decompression surgery. Additionally, we included samples from MS patients (<jats:italic>n<\/jats:italic>\u2009=\u200920) and controls (<jats:italic>n<\/jats:italic>\u2009=\u200920) for comparison.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In both serum and CSF, several proteins were found increased in TN patients compared to either MS patients, controls, or both, including EIF4B, PTPN1, EREG, TBCB, PMVK, FKBP5, CD63, CRADD, BST2, CD302, CRIP2, CCL27, PPP3R1, WWP2, KLB, PLA2G10, TDGF1, SMOC1, RBKS, LTBP3, CLSTN1, NXPH1, SFRP1, HMOX2, and GGT5. The overall expression of the 92 proteins in postoperative TN samples seems to shift towards the levels of MS patients and controls in both serum and CSF, as compared to preoperative samples. Interestingly, there was no difference in protein levels between MS patients and controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We conclude that TN patients showed increased serum and CSF levels of specific proteins and that successful surgery normalizes these protein levels, highlighting its potential as an effective treatment. However, the similarity between MS and controls challenges the idea of shared pathophysiology with TN, suggesting distinct underlying mechanisms in these conditions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>This study advances our understanding of trigeminal neuralgia (TN) and its association with multiple sclerosis (MS). By analysing 92 protein biomarkers, we identified distinctive molecular profiles in TN patients, shedding light on potential pathophysiological mechanisms. The observation that successful surgery normalizes many protein levels suggests a promising avenue for TN treatment. Furthermore, the contrasting protein patterns between TN and MS challenge prevailing assumptions of similarity between the two conditions and point to distinct pathophysiological mechanisms.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ejp.2231","type":"journal-article","created":{"date-parts":[[2023,12,30]],"date-time":"2023-12-30T06:30:21Z","timestamp":1703917821000},"page":"929-942","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Exploring biomarkers in trigeminal neuralgia patients operated with microvascular decompression: A comparison with multiple sclerosis patients and non\u2010neurological controls"],"prefix":"10.1002","volume":"28","author":[{"given":"Muataz S.","family":"Lafta","sequence":"first","affiliation":[{"name":"Department of Surgical Sciences, Functional Pharmacology and Neuroscience Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandr V.","family":"Sokolov","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences, Functional Pharmacology and Neuroscience Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne\u2010Marie","family":"Landtblom","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Neurology Uppsala University  Uppsala Sweden"},{"name":"Department of Biomedical and Clinical Sciences Link\u00f6ping University  Link\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Ericson","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Section of Neurosurgery Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helgi B.","family":"Schi\u00f6th","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences, Functional Pharmacology and Neuroscience Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sami","family":"Abu\u00a0Hamdeh","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Section of Neurosurgery Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,12,29]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2020.03.002"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2014.04.020"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(01)00533-0"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000001061"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.2147\/JPR.S128508"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(20)30233-7"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1479"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI69003"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1055"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1017\/cjn.2017.196"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.15119"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1914484"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST20190334"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2013.08.029"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnana.2016.00095"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00701-016-2994-y"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000001649"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1620\/tjem.221.11"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhy013"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2794"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.7224\/1537-2073.2016-065"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0317167100043225"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2012.12.002"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-018-1103-z"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18122614"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1177\/1744806920901890"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30299-5"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410230214"},{"key":"e_1_2_10_30_1","unstructured":"Gobel H.(2021).13.1.1.3 Idiopathic trigeminal neuralgia.ICHD\u20103.https:\/\/ichd\u20103.org\/13\u2010painful\u2010cranial\u2010neuropathies\u2010and\u2010other\u2010facial\u2010pains\/13\u20101\u2010trigeminal\u2010neuralgia\/13\u20101\u20101\u2010classical\u2010trigeminal\u2010neuralgia\/13\u20101\u20101\u20103\u2010idiopathic\u2010trigeminal\u2010neuralgia\/"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2119630119"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom9010035"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep42621"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2019.09.003"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102413485658"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2008.06332.x"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.3171\/jns.1967.26.1part2.0159"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2006.09.002"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/ane.13243"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1037\/a0033968"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(97)01168-9"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201899456"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00701-013-1970-z"},{"key":"e_1_2_10_44_1","first-page":"1955","article-title":"Outcome after microvascular decompression for trigeminal neuralgia in a single center\u2014Relation to sex and severity of neurovascular conflict","volume":"165","author":"Loayza R.","year":"2023","journal-title":"Acta Neurochirurgica"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.20.010403.113126"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471\u20104159.2006.04328.x"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/124.12.2347"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00234-014-1463-7"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.3171\/2015.2.JNS142587"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102416687280"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.12441"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1016"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/da.22158"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102411424619"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102420974356"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.15252\/embr.202051696"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2015.10.003"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12422"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(01)02326-2"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.167387"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.08.006"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.3171\/JNS-07\/12\/1144"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10194-006-0292-4"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clineuro.2020.106397"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1526-4610.1997.3704211.x"},{"key":"e_1_2_10_66_1","first-page":"998","article-title":"Cerebrospinal fluid in classical trigeminal neuralgia: An exploratory study on candidate biomarkers","volume":"10","author":"Svedung Wettervik T.","year":"2022","journal-title":"Biomedicine"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1003"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1533-2500.2006.00079.x"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002720"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.1111\/gbb.12342"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.09.010"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2011.0118"},{"key":"e_1_2_10_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.01.009"},{"key":"e_1_2_10_74_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD007312.pub2"},{"key":"e_1_2_10_75_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000000853"},{"key":"e_1_2_10_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.11.013"}],"container-title":["European Journal of Pain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ejp.2231","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T08:03:36Z","timestamp":1718697816000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ejp.2231"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,29]]},"references-count":75,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,7]]}},"alternative-id":["10.1002\/ejp.2231"],"URL":"https:\/\/doi.org\/10.1002\/ejp.2231","archive":["Portico"],"relation":{},"ISSN":["1090-3801","1532-2149"],"issn-type":[{"value":"1090-3801","type":"print"},{"value":"1532-2149","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,29]]},"assertion":[{"value":"2023-09-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}