{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T03:54:20Z","timestamp":1791345260205,"version":"4.3.1"},"reference-count":55,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,9,19]],"date-time":"2022-09-19T00:00:00Z","timestamp":1663545600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100020624","name":"NIHR Nottingham Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020624","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012041","name":"Versus Arthritis","doi-asserted-by":"publisher","award":["20777"],"award-info":[{"award-number":["20777"]}],"id":[{"id":"10.13039\/501100012041","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":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Synovial inflammation has known contributions to chronic osteoarthritis (OA) pain, but the potential role in transitions from early to late stages of OA pain is unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The slowly progressing surgical destabilization of the medial meniscus (DMM) murine OA model and sham control, was used in male C57BL\/6J mice to investigate the interplay between knee inflammation, plasma pro\u2010 and anti\u2010inflammatory oxylipins and pain responses during OA progression. Changes in joint histology, macrophage infiltration, chemokine receptor CX3CR1 expression, weight bearing asymmetry, and paw withdrawal thresholds were quantified 4, 8 and 16\u2009weeks after surgery. Plasma levels of multiple bioactive lipid mediators were quantified using liquid chromatography with tandem mass\u2010spectrometry (LC\u2013MS\/MS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Structural joint damage was evident at 8\u2009weeks post\u2010DMM surgery onwards. At 16\u2009weeks post\u2010DMM surgery, synovial scores, numbers of CD68 and CD206 positive macrophages and pain responses were significantly increased. Plasma levels of oxylipins were negatively correlated with joint damage and synovitis scores at 4 and 8\u2009weeks post\u2010DMM surgery. Higher circulating levels of the pro\u2010resolving oxylipin pre\u2010cursor 17\u2010HDHA were associated with lower weight bearing asymmetry at week 16.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The transition to chronic OA pathology and pain is likely influenced by both joint inflammation and plasma oxylipin mediators of inflammation and levels of pro\u2010resolution molecules.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Using a slow progressing surgical model of osteoarthritis we show how the changing balance between local and systemic inflammation may be of importance in the progression of pain behaviours during the transition to chronic osteoarthritis pain.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ejp.2036","type":"journal-article","created":{"date-parts":[[2022,9,13]],"date-time":"2022-09-13T07:33:39Z","timestamp":1663054419000},"page":"2213-2226","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Interplay between cellular changes in the knee joint, circulating lipids and pain behaviours in a slowly progressing murine model of osteoarthritis"],"prefix":"10.1002","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7242-8725","authenticated-orcid":false,"given":"Peter R. W.","family":"Gowler","sequence":"first","affiliation":[{"name":"Pain Centre Versus Arthritis and NIHR Nottingham Biomedical Research Centre, School of Life Sciences University of Nottingham  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Turnbull","sequence":"additional","affiliation":[{"name":"Centre for Analytical Bioscience, Advanced Materials and Healthcare Technologies Division, School of Pharmacy University of Nottingham  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohsen","family":"Shahtaheri","sequence":"additional","affiliation":[{"name":"Pain Centre Versus Arthritis and NIHR Nottingham Biomedical Research Centre, School of Medicine University of Nottingham  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Walsh","sequence":"additional","affiliation":[{"name":"Pain Centre Versus Arthritis and NIHR Nottingham Biomedical Research Centre, School of Medicine University of Nottingham  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Barrett","sequence":"additional","affiliation":[{"name":"Centre for Analytical Bioscience, Advanced Materials and Healthcare Technologies Division, School of Pharmacy University of Nottingham  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Chapman","sequence":"additional","affiliation":[{"name":"Pain Centre Versus Arthritis and NIHR Nottingham Biomedical Research Centre, School of Life Sciences University of Nottingham  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,9,19]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010019\u201041140\u20101"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39279"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1142883"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2009.121426"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD005328.pub2"},{"issue":"9","key":"e_1_2_8_7_1","first-page":"1918","article-title":"Proinflammatory role of fractalkine (CX3CL1) in rheumatoid arthritis","volume":"30","author":"Blaschke S.","year":"2003","journal-title":"The Journal of Rheumatology"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2008.09.018"},{"key":"e_1_2_8_9_1","first-page":"315","volume-title":"Immunity","author":"Buckley C. D.","year":"2014"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010019\u20101471\u20101"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01400"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39523"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14587"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2007.03.006"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000001694"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0239663"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.42000"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.130541"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.40001"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2014.08.012"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1101073108"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2017.01.018"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18112296"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102249.2009.03903.x"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2016.04.010"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0901510"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0508081102"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.34492"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2017.08.006"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2006.11.005"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2009.11.013"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00540\u2010018\u20102579\u20104"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2010.03.002"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.00533"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1209294110"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1063\u20104584(03)00118\u20103"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41583\u2010020\u20100310\u20106"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010physiol\u2010022516\u2010034339"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JOCA.2013.03.018"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5431.1276"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.23884"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2008.087775"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2014.10.008"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2007.03.016"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0206217"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.8.1197"},{"issue":"2","key":"e_1_2_8_47_1","first-page":"365","article-title":"Synovial membrane inflammation and cytokine production in patients with early osteoarthritis","volume":"24","author":"Smith M. D.","year":"1997","journal-title":"Journal of Rheumatology"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.24958"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010017\u201009516\u20103"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.P085118"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.41421"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075\u2010018\u20101751\u20104"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M048694"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep44315"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2020.173090"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01462"}],"container-title":["European Journal of Pain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ejp.2036","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ejp.2036","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ejp.2036","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T12:58:16Z","timestamp":1692536296000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ejp.2036"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,19]]},"references-count":55,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2022,11]]}},"alternative-id":["10.1002\/ejp.2036"],"URL":"https:\/\/doi.org\/10.1002\/ejp.2036","archive":["Portico"],"relation":{},"ISSN":["1090-3801","1532-2149"],"issn-type":[{"value":"1090-3801","type":"print"},{"value":"1532-2149","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,19]]},"assertion":[{"value":"2022-02-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}