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Updated: Jul 25, 2026

An Experimental Paradigm for the Prediction of Post-Operative Pain (PPOP)
Published on: January 27, 2010
Analgesic responses to morphine and placebo in individuals with postoperative pain
Jon D Levine1, Newton C Gordon, Richard Smith
1Department of Neurology, University of California at San Francisco, San Francisco, Calif. 94143, U.S.A. Department of Oral Surgery, University of California at San Francisco, San Francisco, Calif. 94143, U.S.A. Department of Physiology, University of California at San Francisco, San Francisco, Calif. 94143, U.S.A. Division of Rheumatology and Clinical Immunology, University of California at San Francisco, San Francisco, Calif. 94143, U.S.A.
Abstract:
The effects of placebo and varying doses of intravenous morphine were studied in 74 patients. All patients underwent extraction of impacted mandibular third molars. Two hours after onset of anesthesia all patients received a placebo (intravenous saline). One hour after the placebo administration each patient received either a second placebo or, 4, 6, 8 or 12 mg of morphine, double blind, via a hidden intravenous line. Pain level was evaluated 50 min after morphine administration using a visual analog scale. Pooled data from all patients produced a dose-response curve asymptotic by 8 mg. The mean pain relief following the second placebo was found to be between that obtained following hidden administration of 4 and 6 mg of morphine. When pain level reports for individuals were plotted two unexpected features appeared. First, no patient reported complete relief, even at the highest dose of morphine (12 mg). Second, pain level reports 50 min following each dose of morphine tended to be in two clusters. Within each cluster the average pain was independent of the dose of morphine administered. However, in groups receiving progressively higher doses of morphine, the percentage of patients within the low pain level cluster increased. These latter observations are most consistent with the concept that there is a step component for narcotic analgesia.
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