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Pre\u2010clinical laboratory data have supported that a topical formulation of combined diclofenac and methadone (Diclometh) may alleviate local pain, and potentially, the side effect profile should be low. We hypothesized that antiallodynic and antihyperalgesic effects of Diclometh could be demonstrated in a human experimental pain model and that Diclometh would be safe to administer. Thus, the aims were as follows: (i) to compare two doses of Diclometh <jats:italic>versus<\/jats:italic> placebo; and (ii) to assess the safety profile of Diclometh. The study was a crossover, randomized, double\u2010blind, placebo\u2010controlled comparison of two doses of Diclometh gel (0.1% and 0.2%) administered topically in healthy participants. Nerve growth factor (NGF) and capsaicin intradermal injections were used as human pain models. Pressure stimulation, contact heat stimulation, hyperalgesia (pinprick stimulation) and allodynia (brush stimulation) to mechanical stimulation were performed in the area where capsaicin and NGF were injected. Side effects were recorded on a four\u2010point Likert scale. Twenty\u2010one men completed the study (mean age 26.14 \u00b1 5.3). Diclometh 0.2% reduced the capsaicin\u2010induced dynamic mechanical allodynia compared to placebo (primary end\u2010point, <jats:italic>p<\/jats:italic> = 0.03). No other primary or secondary end\u2010points were found significantly different (all <jats:italic>p<\/jats:italic> &gt; 0.05). All side effects were reported as mild with no differences between treatments (<jats:italic>p<\/jats:italic> = 0.15). Indication of antiallodynic effect of Diclometh 0.2% was found. Additionally, it was demonstrated that Diclometh was safe to use.<\/jats:p>","DOI":"10.1111\/bcpt.12993","type":"journal-article","created":{"date-parts":[[2018,3,2]],"date-time":"2018-03-02T12:02:41Z","timestamp":1519992161000},"page":"188-194","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The Effect of a Combination of Diclofenac and Methadone Applied as Gel in a Human Experimental Pain Model \u2013 A Randomized, Placebo\u2010controlled Trial"],"prefix":"10.1111","volume":"123","author":[{"given":"Isabelle M.","family":"Larsen","sequence":"first","affiliation":[{"name":"Mech\u2010Sense Department of Gastroenterology and Hepatology Aalborg University Hospital Aalborg Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asbj\u00f8rn M.","family":"Drewes","sequence":"additional","affiliation":[{"name":"Mech\u2010Sense Department of Gastroenterology and Hepatology Aalborg University Hospital Aalborg Denmark"},{"name":"Department of Clinical Medicine Aalborg University Aalborg Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne E.","family":"Olesen","sequence":"additional","affiliation":[{"name":"Mech\u2010Sense Department of Gastroenterology and Hepatology Aalborg University Hospital Aalborg Denmark"},{"name":"Department of Clinical Medicine Aalborg University Aalborg Denmark"},{"name":"Department of Drug Design and Pharmacology Faculty of Health and Medical Sciences University of Copenhagen Copenhagen 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