ArticlesNaloxone provokes similar pain facilitation as observed after short-term infusion of remifentanil in humansKoppert, Wolfganga; Angst, Martinb; Alsheimer, Monikaa; Sittl, Reinharda; Albrecht, Svena; Schüttler, Jürgena; Schmelz, Martinc,∗Author Information aDepartment of Anesthesiology, University of Erlangen-Nuremberg, Krankenhausstrasse 12, D-91054 Erlangen, Germany bDepartment of Anesthesia, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305–5117, USA cDepartment of Physiology and Experimental Pathophysiology, University of Erlangen-Nuremberg, Universitaetsstrasse 17, D-91054 Erlangen, Germany ∗Corresponding author. Department of Anaesthesiology Mannheim, Clinical Faculty of Medicine Mannheim, University Heidelberg, Theodor-Kutzer Ufer 1–3, D-68135 Mannheim, Germany. Tel.: +49–6121–232–5616; fax: +49–6121–383–2108 E-mail: [email protected] Submitted March 24, 2003; revised July 4, 2003; accepted July 9, 2003. Pain: November 2003 - Volume 106 - Issue 1 - p 91-99 doi: 10.1016/S0304-3959(03)00294-X Buy Metrics Abstract In contrast to an expected preventive analgesic effect, clinical observations suggest that intraoperatively applied opioids can induce postoperative hyperalgesia. We tested the development of post-infusion hyperalgesia in a newly developed experimental model of electrically induced pain and secondary mechanical hyperalgesia. In a double-blind, placebo controlled, cross-over study, 13 subjects received either saline placebo, remifentanil (0.05 or 0.1 μg/kg/min) or naloxone (0.01 mg/kg). Remifentanil dose-dependently reduced pain and mechanical hyperalgesia during the infusion, but upon withdrawal, pain and hyperalgesia increased significantly above control level (p<0.01 and p<0.05, respectively). Naloxone infusion similarly resulted in increased pain (anti-analgesia) (p<0.001) and mechanical hyperalgesia (p<0.01). Increased pain ratings following withdrawal of remifentanil significantly correlated to anti-analgesia evoked by the μ-opioid antagonist naloxone (p<0.01) and was of similar magnitude, suggesting inhibition of endogenous opioids as an underlying mechanism. In contrast, hyperalgesia after remifentanil was more pronounced than hyperalgesia after naloxone administration and did not correlate to the observed anti-analgesic effects, suggesting the involvement of additional receptors systems other than the endorphin system. © 2003 Lippincott Williams & Wilkins, Inc.