{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T02:38:27Z","timestamp":1767926307409,"version":"3.49.0"},"reference-count":62,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,1,25]],"date-time":"2016-01-25T00:00:00Z","timestamp":1453680000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes for Health Research","doi-asserted-by":"crossref","award":["MOP106441"],"award-info":[{"award-number":["MOP106441"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Live Cell Imaging Facility"},{"name":"Snyder Institute at the University of Calgary"},{"name":"Brazilian CNPq postdoctoral fellowship"},{"name":"Natural Sciences and Engineering Research Council of Canada CREATE Training Programme in Host-Parasite Interactions"},{"name":"Canadian Government fellowship"},{"name":"Canadian Institutes for Health Research\/Canadian Association of Gastroenterology\/Janssen Inc. postdoctoral fellowship"},{"DOI":"10.13039\/501100000145","name":"Alberta Innovates Health Solutions postdoctoral fellowship","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000145","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Crohn's and Colitis Foundation of Canada Chair in Inflammatory Bowel Disease Research at Calgary University"},{"name":"Canada Research Chair (Tier 1) in Intestinal Immunophysiology in Health and Disease at the University of Calgary"},{"name":"Mouse Phenomics Core Facility"},{"name":"Snyder Institute for Chronic Diseases"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p><jats:bold> Activation of antiinflammatory cholinergic (vagal) pathways can reduce inflammation, and in vitro studies support a pivotal role of \u03b17 nicotinic acetylcholine receptors (\u03b17\u2010nAChR), macrophages, and T cells in these events. The aim of this study was to assess \u03b17\u2010nAChR agonists  as an antiinflammatory treatment for <\/jats:bold><jats:bold>Freund's complete adjuvant (CFA)\u2013induced monoarthritis.<\/jats:bold><\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Arthritis was induced by intraarticular injection of CFA unilaterally into the knee joints of mice. Animals were treated with \u03b17\u2010nAChR agonists (AR\u2010R17779 or A844606), with or without antagonists (COG133 or methyllycaconitine), and joint inflammation and pain were assessed. Experiments were repeated in c\u2010Kit<jats:sup>W\u2010sh<\/jats:sup> mast cell\u2013deficient mice, and the effects of an \u03b17\u2010nAChR agonist on mast cell proliferation, migration, and activation by lipopolysaccharide (LPS) were tested.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Treatment with \u03b17\u2010nAChR agonists significantly exacerbated CFA\u2010induced arthritis and pain, as gauged by all indices of assessment, the specificity of which was confirmed by coadministration of an nAChR antagonist that attenuated the increase in disease severity. Toluidine blue\u2013positive mast cells were increased in the joint capsule of CFA plus AR\u2010R17779\u2013treated mice, and AR\u2010R17779 enhanced LPS\u2010induced TNF proliferation and migration of a human mast cell line. The AR\u2010R17779\u2013driven increase in severity of CFA\u2010induced arthritis was significantly reduced in mast cell\u2013deficient mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Using CFA to elicit a local inflammatory response, we found that pharmacologic activation of \u03b17\u2010nAChR exacerbated joint inflammation and pain, in part via mast cells, which illustrates the organ\u2010 and disease\u2010specific nature of regulatory neuroimmune mechanisms. Thus, \u03b17\u2010nAChR activation may not be uniformly antiinflammatory in all types of inflammatory joint disease.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.39411","type":"journal-article","created":{"date-parts":[[2015,8,28]],"date-time":"2015-08-28T10:51:23Z","timestamp":1440759083000},"page":"542-552","source":"Crossref","is-referenced-by-count":17,"title":["Involvement of Mast Cells in \u03b17 Nicotinic Receptor Agonist Exacerbation of Freund's Complete Adjuvant\u2013Induced Monoarthritis in Mice"],"prefix":"10.1002","volume":"68","author":[{"given":"Fernando","family":"Lopes","sequence":"first","affiliation":[{"name":"University of Calgary Calgary Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rabea","family":"Graepel","sequence":"additional","affiliation":[{"name":"University of Calgary Calgary Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jose 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