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After ethical approval, 12 healthy male volunteers were included in this randomized, controlled, double\u2010blind, crossover, four\u2010arm study. They were administered intravenous paracetamol (APAP 1\u2003g) or saline (placebo, pl) followed at 100\u2003min with IV naloxone (Nal 8\u2003mg) or saline, every week for 4\u2003weeks. The amplitude of cerebral potentials evoked by thermal\/painful stimuli applied on the arm was recorded nine times over 150\u2003min, witnessing of pain integration at central level. Amplitude changes as well as areas under the curve (AUCs) over 150\u2003min were compared for the four treatments by repeated measures<jats:sc>anova<\/jats:sc>(significance 0.05). Amplitude changes were significant for APAP\/pl vs. pl\/pl at<jats:italic>t<\/jats:italic><jats:sub>150<\/jats:sub>: \u221244% (95%CI \u221258 to \u221230) vs. \u221227% (95%CI \u221237 to \u221217;<jats:italic>P<\/jats:italic>\u2003&lt;\u20030.05) but not vs. APAP\/Nal. AUC (0\u2013150) of APAP\/pl is significantly different from pl\/pl (\u22123452%.min (95%CI \u22124705 to \u22122199) vs. \u2212933% min (95%CI \u22122273 to 407;<jats:italic>P<\/jats:italic>\u2003=\u20030.015) but not from APAP\/Nal (\u22121731% min (95%CI \u22123676 to 214;<jats:italic>P<\/jats:italic>\u2003=\u20030.08) and other treatments. AUC (90\u2013150) is not significantly different. This pilot study shows for the first time in human volunteers that naloxone does not inhibit paracetamol antinociception, suggesting no significant implication of the opioid system in paracetamol mechanism of action: this needs be confirmed on a larger number of subjects.<\/jats:p>","DOI":"10.1111\/j.1472-8206.2011.01010.x","type":"journal-article","created":{"date-parts":[[2011,11,18]],"date-time":"2011-11-18T03:15:19Z","timestamp":1321586119000},"page":"339-345","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Paracetamol and opioid pathways: a pilot randomized clinical trial"],"prefix":"10.1111","volume":"27","author":[{"given":"Gis\u00e8le","family":"Pickering","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fares","family":"Moustafa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Desbrandes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Michel Cardot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delphine","family":"Roux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claude","family":"Dubray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,11,17]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199507310-00020"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(02)01578-9"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(91)90036-P"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(96)00261-0"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2005.01.019"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/240410a0"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2008.03.030"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-006-6113-z"},{"key":"e_1_2_6_10_2","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1016\/S0022-3565(24)36432-8","article-title":"Naloxone\u2010reversible antinociception by paracetamol in the rat","volume":"280","author":"Pini L.A.","year":"1997","journal-title":"JPET"},{"key":"e_1_2_6_11_2","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/S0022-3565(24)38900-1","article-title":"Discovery of \u201cself\u2010synergistic\u201d spinal\/supraspinal antinociception produced by acetaminophen (paracetamol)","volume":"295","author":"Raffa R.B.","year":"2000","journal-title":"J. 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