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.

The manifestation of an allergic reaction ranges from urticaria and rash to severe bronchoconstriction, laryngeal edema, hematological disorders, and other serious maladies. Many drugs, especially penicillins, β-lactam antibiotics, and sulfonamides, given in the perioperative setting, induce allergic reactions (1). Although true allergic reactions to opioids are rare, naturally occurring compounds such as morphine and codeine can cause allergic reactions and can even lead to anaphylactic shock (2, 3), whereas reactions to semi-synthetic and synthetic compounds are seldom seen. Opioid-receptor agonists and antagonists have been tested on their ability to induce mast cell degranulation in the skin (4, 5). In in vitro settings, morphine liberated histamine and tryptase from mast cells isolated from skin (HSMC), whereas buprenorphine did so only from mast cells isolated from lung parenchyma (HLMC), and fentanyl was not able to liberate mediators from any kind of mast cell (6). Severe itching and reddening of the skin, especially around the site of IM or subcutaneous injections of morphine, have been documented. Mast cell degranulation and the consecutive release of vasoactive mediators such as histamine are regarded as the main mechanisms (7). After the epidural injection of morphine, generalized or segmental itch sensations occur that can be attenuated by histamine antagonists, eg, promethazine (8). Whether the degranulation of cutaneous mast cells by opioids depends on an agonistic effect on opioid μ receptors is still not clear. Experiments with opioid receptor antagonists (naloxone), morphine, meperidine, and codeine suggest that both opioid and non-opioid receptors may be involved (9).