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However, dosing and differential effects on peripheral and central hyperalgesia are still to be determined. After <jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>thics <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>ommittee approval, 32 volunteers have been included in this 2 phased, double blinded, placebo controlled, cross\u2010over study. A defined small skin area was irradiated with a <jats:styled-content style=\"fixed-case\">UVB<\/jats:styled-content> source inducing hyperalgesia. Twenty\u2010four hours after irradiation, heat pain\u2010, cold pain threshold (<jats:styled-content style=\"fixed-case\">HPPT<\/jats:styled-content>, <jats:styled-content style=\"fixed-case\">CPPT<\/jats:styled-content>), mechanical pain sensitivity to pin prick (<jats:styled-content style=\"fixed-case\">MPS<\/jats:styled-content>) in the area of pin prick hyperalgesia (<jats:styled-content style=\"fixed-case\">AsH<\/jats:styled-content>) and <jats:styled-content style=\"fixed-case\">MPS<\/jats:styled-content> in the sunburn were determined. In phase <jats:styled-content style=\"fixed-case\">I<\/jats:styled-content>, measurements have been repeated 30\u2009min after receiving cumulative 0.3, 0.6 and 1\u2009mg\/kg of intravenous (<jats:italic>i.v.<\/jats:italic>) tramadol or active placebo. Only at 1\u2009mg\/kg tramadol and solely for <jats:styled-content style=\"fixed-case\">MPS<\/jats:styled-content> in the sunburn a reduction to placebo could be demonstrated (<jats:italic>p<\/jats:italic>\u2009=\u20090.024). Accordingly in phase <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content>, the trial has been repeated using 1\u2009mg\/kg tramadol and paracetamol or placebo in a cumulative <jats:italic>i.v.<\/jats:italic> dose of 330, 660 and 990\u2009mg. Now the addition of 330\u2009mg paracetamol to tramadol reduced thermal hyperalgesia by 1.15\u2009\u00b0C (<jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 0.55; 1.76). This effect, however, did not increase with higher doses. Tramadol showed week anti\u2010hyperalgesia reducing <jats:styled-content style=\"fixed-case\">CPPT<\/jats:styled-content>, <jats:styled-content style=\"fixed-case\">MPS<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">AsH<\/jats:styled-content> compared to baseline measurements (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Paracetamol also reduced secondary hyperalgesia, but no combination effect with tramadol could be shown. We conclude, in inflammatory hyperalgesia tramadol alone exerts only weak anti\u2010hyperalgesia. Even adding a small dose paracetamol enhances thermal anti\u2010hyperalgesia.<\/jats:p>","DOI":"10.1016\/j.ejpain.2011.08.007","type":"journal-article","created":{"date-parts":[[2011,9,11]],"date-time":"2011-09-11T13:46:53Z","timestamp":1315748813000},"page":"562-573","source":"Crossref","is-referenced-by-count":11,"title":["Dose response of tramadol and its combination with paracetamol in <scp>UVB<\/scp> induced hyperalgesia"],"prefix":"10.1002","volume":"16","author":[{"given":"C.M.","family":"Ortner","sequence":"first","affiliation":[{"name":"Department of Anesthesiology General Intensive Care and Pain Control Vienna Human Pain Research Group Medical University Vienna  Vienna Austria"},{"name":"Department of Anesthesiology and Pain Medicine University of Washington  Seattle WA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I.","family":"Steiner","sequence":"additional","affiliation":[{"name":"Institute for Medical Statistics Medical University Vienna  Vienna 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