Opioid-induced mast cell activation and vascular responses is not mediated by mu-opioid receptors: an in vivo microdialysis study in human skin.
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 mu-opioid receptors are involved in the activation of mast cells.


CONCLUSIONS
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 micro agonists is caused by an unspecific effect rather than an activation of opioid receptors.
Blunk
James A
JA
*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.
Schmelz
Martin
M
Zeck
Susanne
S
Skov
Per
P
Likar
Rudolf
R
Koppert
Wolfgang
W
D000328:Adult; D000701:Analgesics, Opioid / Q000494:pharmacology*; D001808:Blood Vessels / Q000187:drug effects*; D002199:Capillary Permeability / Q000187:drug effects; D015550:Cell Degranulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004890:Erythema / Q000473:pathology; D005260:Female; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D008297:Male; D008407:Mast Cells / Q000187:drug effects*; D017551:Microdialysis; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D017450:Receptors, Opioid, mu / Q000187:drug effects*; D012039:Regional Blood Flow / Q000187:drug effects; D012697:Serine Endopeptidases / Q000378:metabolism; D012867:Skin / Q000098:blood supply / Q000166:cytology / Q000187:drug effects*; D053802:Tryptases
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D017450:Receptors, Opioid, mu; D009270:Naloxone; D012697:Serine Endopeptidases; D053802:Tryptases