{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:01:05Z","timestamp":1791302465641,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"2b","license":[{"start":{"date-parts":[[2011,8,28]],"date-time":"2011-08-28T00:00:00Z","timestamp":1314489600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2011,9,2]]},"abstract":"<jats:p><jats:bold>BACKGROUND AND PURPOSE<\/jats:bold> We investigated the effect of the phosphodiesterase\u20105 inhibitor, tadalafil, on the acute hypernociception in rat models of arthritis.<\/jats:p><jats:p><jats:bold>EXPERIMENTAL APPROACH<\/jats:bold> Rats were treated with either an intra\u2010articular injection of zymosan (1\u2003mg) or surgical transection of the anterior cruciate ligament (as an osteoarthritis model). Controls received saline intra\u2010articular or sham operation respectively. Joint pain was evaluated using the articular incapacitation test measured over 6\u2003h following zymosan or between 4 and 7 days after anterior cruciate ligament transection. Cell counts, tumour necrosis factor\u2010\u03b1 (TNF\u2010\u03b1), interleukin\u20101 (IL\u20101), and the chemokine, cytokine\u2010induced neutrophil chemoattractant\u20101 (CINC\u20101) were measured in joint exudates 6\u2003h after zymosan. Groups received tadalafil (0.02\u20130.5\u2003mg\u00b7kg<jats:sup>\u22121<\/jats:sup><jats:italic>per os<\/jats:italic>) or saline 2\u2003h after intra\u2010articular zymosan. Other groups received the \u00b5\u2010opioid receptor antagonist naloxone or the cGMP inhibitor 1H\u2010[1,2,4] oxadiazolo [4,3\u2010a] quinoxalin\u20101\u2010one (ODQ) before tadalafil.<\/jats:p><jats:p><jats:bold>KEY RESULTS<\/jats:bold> Tadalafil dose\u2010dependently inhibited hypernociception in zymosan and osteoarthritis models. In zymosan\u2010induced arthritis, tadalafil significantly decreased cell influx and TNF\u2010\u03b1 release but did not alter IL\u20101 or CINC\u20101 levels. Pretreatment with ODQ but not with naloxone prevented the anti\u2010inflammatory effects of tadalafil.<\/jats:p><jats:p><jats:bold>CONCLUSIONS AND IMPLICATIONS<\/jats:bold> Therapeutic oral administration of tadalafil provided analgesia mediated by guanylyl cyclase and was independent of the release of endogenous opioids. This effect of tadalafil was associated with a decrease in neutrophil influx and TNF\u2010\u03b1 release in inflamed joints.<\/jats:p>","DOI":"10.1111\/j.1476-5381.2011.01469.x","type":"journal-article","created":{"date-parts":[[2011,5,10]],"date-time":"2011-05-10T11:02:22Z","timestamp":1305025342000},"page":"828-835","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Tadalafil analgesia in experimental arthritis involves suppression of intra\u2010articular TNF release"],"prefix":"10.1111","volume":"164","author":[{"given":"FAC","family":"Rocha","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"FS","family":"Silva 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