{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T19:04:51Z","timestamp":1790535891420,"version":"4.1.0"},"reference-count":56,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,11,15]],"date-time":"2017-11-15T00:00:00Z","timestamp":1510704000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100010344","name":"Scan|Design Foundation by Inger and Jens Bruun","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010344","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pain Practice"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Impaired pain inhibitory and enhanced pain facilitatory mechanisms are repeatedly reported in patients with central sensitization pain. However, the exact effects of frequently prescribed opioids on central pain modulation are still unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A randomized, double\u2010blind, placebo\u2010controlled cross\u2010over trial was carried out. Ten chronic fatigue syndrome (<jats:styled-content style=\"fixed-case\">CFS<\/jats:styled-content>)\/fibromyalgia (<jats:styled-content style=\"fixed-case\">FM<\/jats:styled-content>) patients, 11 rheumatoid arthritis (<jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>) patients and 20 controls were randomly allocated to the experimental (10\u00a0mg morphine or 0.2\u00a0mg\/mL Naloxone) and placebo (2\u00a0mL Aqua) group. Pressure pain thresholds (<jats:styled-content style=\"fixed-case\">PPT<\/jats:styled-content>s) and temporal summation at the Trapezius and Quadriceps were assessed by algometry. Conditioned pain modulation (<jats:styled-content style=\"fixed-case\">CPM<\/jats:styled-content>) efficacy and deep tissue pain pressure were assessed by adding ischemic occlusion at the opposite upper arm.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Deep tissue pain pressure was lower and temporal summation higher in <jats:styled-content style=\"fixed-case\">CFS<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">FM<\/jats:styled-content> (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.002 respectively <jats:italic>P<\/jats:italic>\u00a0=\u00a00.010) and <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content> patients (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.011 respectively <jats:italic>P<\/jats:italic>\u00a0=\u00a00.047) compared to controls at baseline. Morphine had only a positive effect on <jats:styled-content style=\"fixed-case\">PPT<\/jats:styled-content>s in both patient groups (<jats:italic>P<\/jats:italic>\u00a0time\u00a0=\u00a00.034). Accordingly, <jats:styled-content style=\"fixed-case\">PPT<\/jats:styled-content>s increased after placebo (<jats:italic>P<\/jats:italic> time\u00a0=\u00a00.015), and no effects on the other pain parameters\u00a0were objectified. There were no significant effects of naloxone nor nocebo on <jats:styled-content style=\"fixed-case\">PPT<\/jats:styled-content>, deep tissue pain, temporal summation or <jats:styled-content style=\"fixed-case\">CPM<\/jats:styled-content> in the control group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study revealed anti\u2010hyperalgesia effects of morphine in <jats:styled-content style=\"fixed-case\">CFS<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">FM<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content> patients. Nevertheless, these effects were comparable to placebo. Besides, neither morphine nor naloxone influenced deep tissue pain, temporal summation or <jats:styled-content style=\"fixed-case\">CPM<\/jats:styled-content>. Therefore, these results suggest that the opioid system is not dominant in (enhanced) bottom\u2010up sensitization (temporal summation) or (impaired) endogenous pain inhibition (<jats:styled-content style=\"fixed-case\">CPM<\/jats:styled-content>) in patients with <jats:styled-content style=\"fixed-case\">CFS<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">FM<\/jats:styled-content> or <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/papr.12613","type":"journal-article","created":{"date-parts":[[2017,7,19]],"date-time":"2017-07-19T14:13:00Z","timestamp":1500473580000},"page":"418-430","source":"Crossref","is-referenced-by-count":33,"title":["Influence of Morphine and Naloxone on Pain Modulation in Rheumatoid Arthritis, Chronic Fatigue Syndrome\/Fibromyalgia, and Controls: A Double\u2010Blind, Randomized, Placebo\u2010Controlled, Cross\u2010Over Study"],"prefix":"10.1111","volume":"18","author":[{"given":"Linda","family":"Hermans","sequence":"first","affiliation":[{"name":"Department of Rehabilitation Sciences and Physiotherapy Faculty of Medicine and Health Sciences Ghent University Ghent Belgium"},{"name":"Pain in Motion International Research Group Vrije Universiteit Brussel Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo","family":"Nijs","sequence":"additional","affiliation":[{"name":"Pain in Motion International Research Group Vrije Universiteit Brussel Brussels Belgium"},{"name":"Department of Physiotherapy, Human Physiology and Anatomy Faculty of Physical Education and Physiotherapy Vrije Universiteit Brussel Brussels Belgium"},{"name":"Department of Rehabilitation and Physiotherapy University Hospital Brussels Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Calders","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Sciences and Physiotherapy Faculty of Medicine and Health Sciences Ghent University Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc","family":"De Clerck","sequence":"additional","affiliation":[{"name":"Department of Immunology, Allergy and Rheumatology University of Antwerp Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greta","family":"Moorkens","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University Hospital Antwerp Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Hans","sequence":"additional","affiliation":[{"name":"Multidisciplinary Pain Center University Hospital Antwerp Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofie","family":"Grosemans","sequence":"additional","affiliation":[{"name":"Multidisciplinary Pain Center University Hospital Antwerp Antwerp 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