{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T10:30:12Z","timestamp":1790245812040,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,1,12]],"date-time":"2015-01-12T00:00:00Z","timestamp":1421020800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"National Science Center","award":["DEC-2011\/03\/N\/NZ4\/03765"],"award-info":[{"award-number":["DEC-2011\/03\/N\/NZ4\/03765"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2015,2]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Some studies suggest that 5\u2010lipoxygenase (5\u2010<jats:styled-content style=\"fixed-case\">LOX<\/jats:styled-content>) inhibition or leukotriene receptor antagonism may effectively attenuate different kinds of pain. In the present study, we investigated whether esculetin (which, among other actions, potently inhibits 5\u2010<jats:styled-content style=\"fixed-case\">LOX<\/jats:styled-content>) possesses analgesic activity in acute non\u2010inflammatory pain and acute inflammatory pain models in rats. We also examined the effects of zileuton, a selective 5\u2010<jats:styled-content style=\"fixed-case\">LOX<\/jats:styled-content> inhibitor, on esculetin activity. Plasma concentrations of leukotriene B<jats:sub>4<\/jats:sub> (<jats:styled-content style=\"fixed-case\">LTB<\/jats:styled-content><jats:sub>4<\/jats:sub>) after administration of esculetin were also determined. Esculetin (1.25\u201320\u00a0mg\/kg, i.p.) dose\u2010dependently alleviated hyperalgesia and exhibited antinociceptive effects in both experimental models. The greatest effect of esculetin was observed with a dose of 20\u00a0mg\/kg. In carrageenan\u2010induced inflammatory pain in rats, 20\u00a0mg\/kg esculetin reversed or mitigated hyperalgesia, increasing the threshold to mechanical stimuli from a control value of \u221223.8\u00a0\u00b1\u00a01.8% to 15.2\u00a0\u00b1\u00a02.2% (<jats:italic>P\u00a0<\/jats:italic>&lt;\u00a00.01) and that to thermal stimuli from \u221252.5\u00a0\u00b1\u00a06.1% to \u22129.5\u00a0\u00b1\u00a03.9% (<jats:italic>P\u00a0<\/jats:italic>&lt;\u00a00.01). In non\u2010inflammatory pain, after esculetin (20\u00a0mg\/kg) administration the threshold values to mechanical and thermal stimuli increased to 75.9\u00a0\u00b1\u00a04.2% and 59.2\u00a0\u00b1\u00a04.3%, respectively (<jats:italic>P\u00a0<\/jats:italic>&lt;\u00a00.01 for both). Zileuton (30\u00a0mg\/kg, p.o.) alone slightly but significantly increased the pain threshold in the non\u2010inflammatory and inflammatory acute pain models. Pretreatment with 30\u00a0mg\/kg, p.o., zileuton significantly enhanced the analgesic activity of 5\u00a0mg\/kg, i.p., esculetin in both pain models. Moreover, esculetin (10\u00a0mg\/kg, i.p.) decreased <jats:styled-content style=\"fixed-case\">LTB<\/jats:styled-content><jats:sub>4<\/jats:sub> concentrations in the blood from 244\u00a0\u00b1\u00a029\u00a0pg\/mL in the control group to 185\u00a0\u00b1\u00a011\u00a0pg\/mL (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.005). The results of the present study suggest the involvement of the 5\u2010<jats:styled-content style=\"fixed-case\">LOX<\/jats:styled-content> pathway in esculetin analgesia.<\/jats:p>","DOI":"10.1111\/1440-1681.12346","type":"journal-article","created":{"date-parts":[[2014,11,25]],"date-time":"2014-11-25T13:35:55Z","timestamp":1416922555000},"page":"213-219","source":"Crossref","is-referenced-by-count":22,"title":["Antinociceptive properties of esculetin in non\u2010inflammatory and inflammatory models of pain in rats"],"prefix":"10.1111","volume":"42","author":[{"given":"Przemyslaw","family":"Rzodkiewicz","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Institute of Rheumatology Warsaw Poland"},{"name":"Department of Pharmacodynamics Centre for Preclinical Research and Technology Medical University of Warsaw Warsaw 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