naloxone and Erythema

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.. 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.

Topics: Adult; Analgesics, Opioid; Blood Vessels; Capillary Permeability; Cell Degranulation; Dose-Response Relationship, Drug; Double-Blind Method; Erythema; Female; Histamine Release; Humans; Male; Mast Cells; Microdialysis; Naloxone; Narcotic Antagonists; Receptors, Opioid, mu; Regional Blood Flow; Serine Endopeptidases; Skin; Tryptases

HR-1 hairless mice fed with a special diet develop atopic-like dry skin, characterized by increased transepidermal water loss, and prolonged bouts of spontaneous scratching. In this study, the role of the skin barrier dysfunction in the prolongation of scratching was evaluated. Although the prolonged scratching was dose-dependently inhibited by opioid receptor antagonist naloxone, neither H(1) receptor antagonist, mepyramine, nor 5-HT(1/2) receptor antagonist, methysergide, affected it. Thus, the prolonged scratching could be itch-related response independent of histamine and serotonin. The application of petrolatum ointment on the skin temporarily alleviated the increase of transepidermal water loss for 60 min after treatment. Due to this alleviation in barrier dysfunction, the prolongation of scratching was significantly suppressed. However, when the barrier dysfunction relapsed, the scratching worsened. Taken together, a skin barrier dysfunction is associated with the itch-related response.

Topics: Animals; Behavior, Animal; Dermatitis, Atopic; Dose-Response Relationship, Drug; Epidermis; Erythema; Female; Food, Formulated; Injections, Intraperitoneal; Injections, Subcutaneous; Methysergide; Mice; Mice, Hairless; Naloxone; Ointments; Petrolatum; Pruritus; Pyrilamine; Recurrence; Skin Diseases; Time Factors; Water Loss, Insensible

We evaluated the ability of morphine to release histamine when injected intradermally in man. Mathematic analysis of the dose-response (wheal) relationship suggested that two different effects were involved. The effect of low doses of morphine (0.05 to 1 microgram) was clearly antagonized by naloxone (0.4 or 1.2 mg im 30 minutes before), whereas the effect of higher doses (5 to 50 micrograms) was not modified. The median effective doses of morphine (ED50) for the low dose range effect were 0.07 +/- 0.01 and 0.08 +/- 0.01 microgram before naloxone and 0.14 +/- 0.02 and 0.15 +/- 0.03 microgram after 0.4 and 1.2 mg doses, respectively. Astemizole (45 mg po 30 minutes before) and oxatomide (60 mg po 120 minutes before) produced similar inhibition of histamine-induced wheals, but there were clear differences in their effects on wheals elicited by morphine. Morphine ED50 values for the low dose range effect rose from 0.09 +/- 0.01 to 0.20 +/- 0.01 microgram after astemizole and from 0.08 +/- 0.01 to 0.46 +/- 0.04 microgram after oxatomide. Opiate receptors may be involved in some of the effects produced by morphine injection in the human skin, but morphine-induced wheals seem to offer a suitable model for the evaluation of agents capable of inhibiting histamine release in man.

Topics: Adult; Astemizole; Benzimidazoles; Dose-Response Relationship, Drug; Drug Interactions; Erythema; Histamine Release; Humans; Injections, Intradermal; Male; Morphine; Naloxone; Piperazines