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ANESTHETIC PHARMACOLOGY

Opioid-Induced Mast Cell Activation and Vascular Responses Is Not Mediated by µ-Opioid Receptors: An In Vivo Microdialysis Study in Human Skin

James A. Blunk, MD^*, Martin Schmelz, MD, Susanne Zeck, MD^*, Per Skov, MD, Rudolf Likar, MD, and Wolfgang Koppert, MD^*

*Department of Anesthesiology, University Hospital, Erlangen; Department of Anesthesiology and Critical Care Medicine Mannheim, University Heidelberg, Germany; The Reference Laboratory, University Hospital Kopenhagen, Denmark; and Department of Anesthesiology, LKH Klagenfurt, Austria

Address correspondence and reprint requests to James Blunk, Department of Physiology and Experimental Pathophysiology, University of Erlangen-Nuremberg, Universitätsstraße 17, D-91054 Erlangen, Germany. Address e-mail to blunk{at}physiologie1.uni-erlangen.de

Activation of mast cells and the systemic release of histamine is a common side effect of opioids. Nevertheless, fentanyl and its derivatives show only a slight activation of mast cells with a subsequent liberation of histamine and tryptase. In this study, we used intradermal microdialysis to assess whether this stimulatory effect of opioids on mast cells depends on the activation of opioid receptors. This new approach allowed us to measure the dose-dependent release of histamine and tryptase from mast cells and the subsequent vascular and sensory effect without systemic side effects in volunteers. The opiate codeine and the synthetic opioids meperidine, fentanyl, alfentanil, sufentanil, remifentanil, buprenorphine, and the opioid antagonist naloxone were tested. Only codeine and meperidine induced mast cell activation with the release of tryptase and histamine, leading to protein extravasation, flare reactions, and itch sensations. Because naloxone did not attenuate these effects, it is unlikely that µ-opioid receptors are involved in the activation of mast cells.

IMPLICATIONS: Opioid effects on mast cells were assessed using intradermal microdialysis. Mast cell activation was seen with codeine and meperidine; no other opioid induced degranulation. Therefore, histamine release seen at large concentrations of potent µ agonists is caused by an unspecific effect rather than an activation of opioid receptors.

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999