{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T08:12:00Z","timestamp":1778919120307,"version":"3.51.4"},"reference-count":54,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008368","name":"Gigtforeningen","doi-asserted-by":"publisher","award":["R204\u2010A7645"],"award-info":[{"award-number":["R204\u2010A7645"]}],"id":[{"id":"10.13039\/100008368","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pain"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>This exploratory study investigates if intra\u2010articular injected gold microparticles in knee osteoarthritis (KOA) reduce immunomodulatory\u2010based pain via proteomic changes in the synovial fluid (SF) and serum.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Thirty patients with moderate KOA were included. Intraarticular injections with 20\u00a0mg gold microparticles (72.000 particles, 20\u201340\u00a0\u00b5m in diameter) using the patient's synovial fluid (SF) as carrier were performed. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) subscores for pain, stiffness, and function were assessed at inclusion, 8\u00a0weeks and 2\u00a0years The PainDetect questionnaire, pain pressure threshold (PPT), temporal summation (TS), and conditioned pain modulation (CPM), and pain diary were assessed at inclusion and 8\u00a0weeks. Proteome analysis was performed on SF and blood samples before and after 8\u00a0weeks of treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A decrease in WOMAC scores (pain (<jats:italic>p\u00a0<\/jats:italic>=\u00a00.0001), stiffness (<jats:italic>p\u00a0<\/jats:italic>=\u00a00.0088), activity (<jats:italic>p\u00a0<\/jats:italic>=\u00a00.0001)), PainDetect (<jats:italic>p\u00a0<\/jats:italic>=\u00a00.0002) and increase in PPT (<jats:italic>p\u00a0<\/jats:italic>=\u00a00.001) and CPM (<jats:italic>p\u00a0<\/jats:italic>=\u00a00.021) and a decrease in TS (<jats:italic>p\u00a0<\/jats:italic>=\u00a00.03) were found after 8\u00a0weeks compared to inclusion assessments. At 2\u00a0years follow\u2010up compared to baseline there was a decrease in WOMAC scores (pain (<jats:italic>p\u00a0<\/jats:italic>=\u00a00.0001), stiffness (<jats:italic>p\u00a0<\/jats:italic>=\u00a00.007), activity (<jats:italic>p\u00a0<\/jats:italic>=\u00a00.0001)) and PainDetect (<jats:italic>p\u00a0<\/jats:italic>=\u00a00.0001). In SF, 28 different proteins were downregulated and 11 upregulated (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05) mainly associated immune response. Similarly, 31 proteins were downregulated and 1 upregulated in serum (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05) reflecting key immune response and anatomical structure development processes. No adverse effects related to the treatment were recorded.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Gold microparticles injected intra\u2010articular in KOA joints may provide pain relief and an inflammatory modulatory effect based on proteome changes found in SF and serum. A randomized, controlled, double\u2010blind study is needed to infer a conclusion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>This study indicates that intra\u2010articular gold may provide advantages in clinical practice for managing knee osteoarthritic pain. The use of intraarticular gold can add new knowledge to the treatment of inflammation and pain.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ejp.1909","type":"journal-article","created":{"date-parts":[[2022,1,25]],"date-time":"2022-01-25T10:21:58Z","timestamp":1643106118000},"page":"811-824","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Gold micro\u2010particles for knee osteoarthritis"],"prefix":"10.1002","volume":"26","author":[{"given":"Sten","family":"Rasmussen","sequence":"first","affiliation":[{"name":"Department of Clinical Medicine Aalborg University  Aalborg Denmark"},{"name":"Department of Orthopedic Surgery, Sport and Arthroscopy Aalborg University Hospital  Aalborg Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristian","family":"Kj\u00e6r Petersen","sequence":"additional","affiliation":[{"name":"Department of Health Science and Technology Aalborg University  Aalborg Denmark"},{"name":"Department of Health Science and Technology Faculty of Medicine Center for Neuroplasticity and Pain Aalborg University  Aalborg Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin Kaae","family":"Kristiansen","sequence":"additional","affiliation":[{"name":"Department of Health Science and Technology Aalborg University  Aalborg Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jakob","family":"Skallerup","sequence":"additional","affiliation":[{"name":"Department of Health Science and Technology Aalborg University  Aalborg Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Aboo","sequence":"additional","affiliation":[{"name":"Department of Health Science and Technology Aalborg University  Aalborg Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikkel Eggert","family":"Thomsen","sequence":"additional","affiliation":[{"name":"Department of Health Science and Technology Aalborg University  Aalborg Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emilie","family":"Skjoldemose","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine Aalborg University  Aalborg Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nia Kristine","family":"J\u00f8rgensen","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine Aalborg University  Aalborg Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allan","family":"Stensballe","sequence":"additional","affiliation":[{"name":"Department of Health Science and Technology Aalborg University  Aalborg Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars","family":"Arendt\u2010Nielsen","sequence":"additional","affiliation":[{"name":"Department of Health Science and Technology Aalborg University  Aalborg Denmark"},{"name":"Department of Health Science and Technology Faculty of Medicine Center for Neuroplasticity and Pain Aalborg University  Aalborg Denmark"},{"name":"Department of Medical Gastroenterology Mech\u2010Sense Aalborg University Hospital  Aalborg Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,2]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000000562"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.berh.2010.01.013"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11914-015-0276-x"},{"key":"e_1_2_8_5_1","first-page":"1833","article-title":"Validation study of WOMAC: A health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee","volume":"15","author":"Bellamy N.","year":"1988","journal-title":"Journal of Rheumatology"},{"key":"e_1_2_8_6_1","first-page":"CD005328","article-title":"Intraarticular corticosteroid for treatment of osteoarthritis of the knee","volume":"10","author":"Bellamy N.","year":"2006","journal-title":"Cochrane Database Systematic Review"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1039\/c1mt00062d"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12014-020-09292-9"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38279"},{"key":"e_1_2_8_10_1","first-page":"CD000520","article-title":"Injectable gold for rheumatoid arthritis (Review)","volume":"1997","author":"Clark P.","year":"2010","journal-title":"Cochrane Database Systematic Reviews"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-002-0400-8"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-010-0681-2"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2019.00451"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1185\/030079906X132488"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/AJP.0000000000000804"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00076-18"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2007.03469.x"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/956169"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12891-019-2667-0"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.3380"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/1751-0147-49-9"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/ani2030426"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1179\/jmt.2009.17.3.163"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.16.4.494"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1080\/21691401.2018.1446968"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.8b00483"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40814-019-0499-1"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-008-0448-1"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22063279"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.21018"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.201601343"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1177\/0300985810381910"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22031448"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jevs.2017.03.005"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-020-00998-0"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm8091343"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-008-0918-9"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi982198u"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2017.02.002"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-012-0996-2"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.0000000000000022"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000001427"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1097\/AJP.0000000000000334"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejp.1465"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000002019"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2004.02.001"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-004-0869-8"},{"key":"e_1_2_8_48_1","first-page":"11","article-title":"Analysis of high accuracy, quantitative proteomics data in the MaxQB database","author":"Schaab C.","year":"2012","journal-title":"Molecular & Cellular Proteomics: MCP"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0300-9475.2004.01507.x"},{"key":"e_1_2_8_50_1","first-page":"9","article-title":"Gene expression profiling of macrophages: Implications for an immunosuppressive effect of dissolucytotic gold ions","author":"Seifert O.","year":"2012","journal-title":"J Inflamm (United Kingdom)"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2013.10.020"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2021.01.015"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.111203"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1700897"},{"key":"e_1_2_8_55_1","article-title":"Metascape provides a biologist\u2010oriented resource for the analysis of systems\u2010level datasets","author":"Zhou Y.","year":"2019","journal-title":"Nature Communications"}],"container-title":["European Journal of Pain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ejp.1909","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ejp.1909","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ejp.1909","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,27]],"date-time":"2023-08-27T05:54:10Z","timestamp":1693115650000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ejp.1909"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2]]},"references-count":54,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2022,4]]}},"alternative-id":["10.1002\/ejp.1909"],"URL":"https:\/\/doi.org\/10.1002\/ejp.1909","archive":["Portico"],"relation":{},"ISSN":["1090-3801","1532-2149"],"issn-type":[{"value":"1090-3801","type":"print"},{"value":"1532-2149","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2]]},"assertion":[{"value":"2021-09-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-02-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}