Potentiation of histamine-induced itch and flare responses in human skin by the enkephalin analogue FK 33-824, ?-endorphin and morphine

Abstract

The effect of various opioid or putative neurotransmitter peptides on histamine-induced itch and flare responses was studied in humans after intradermal injection. Significant enhancement of the histamine responses was induced by the stable methionine-enkephalin analogue FK 33-824, beta-endorphin and morphine. The putative neurotransmitters substance P and vasoactive intestinal polypeptide (VIP)--which moreover are potent histamine liberators--had no enhancing effect. The potentiation induced by FK 33-824 was induced neither by local pretreatment with Compound 48/80 to deplete the local stores of mast-cell-bound histamine, nor by oral pretreatment with indomethacin to inhibit prostaglandin formation in the skin. Thus, the enhancement did not seem to be due to histamine release or to prostaglandin formation and the mechanism of the effect remains to be shown. The specific morphine antagonist naloxone did not inhibit the potentiation by FK 33-824, which might indicate that ordinary opiate receptors were not involved. The results support the idea that pain and itch are qualitatively separate processes and suggest possible mechanisms of morphine-induced pruritus. The findings are of particular interest in view of recent reports on the presence of methionine-enkephalin in Merkel cells.

Pruritic dermatoses: overview of etiology and therapy

“…Evidence increasingly suggests that endogenous opioids (endorphins) may be involved in transmission of itch. 22 …”

Anaesthesia for daycase gynaecological laparoscopy: a survey of clinical practice in the United Kingdom

“…Ninety per cent of consultant anaesthetists use inhalational agents for maintenance of anaesthesia in daycase laparoscopy patients, 50% do not employ any form of adjunctive local anaesthetic technique while a small proportion (6%) do not use NSAIDs wherever possible. Since the principal reasons for overnight admission following daycase gynaecological laparoscopy are pain, nausea and vomiting, dizziness and delayed mobilisation [3,4], we feel that these areas warrant further discussion.…”

“…Pruritus is a subjective unpleasant sensation arising from irritation of the nociceptor fibres in the superficial layers of the skin which provokes the urge to scratch. It is common following opioid administration and may be more unpleasant than the pain itself [1][2][3][4]. While pruritus has been reported following intravenous or intramuscular administration, it has been suggested that it is most common following intrathecal or epidural administration of opioids [5,6].…”

“…However, laparoscopy under general anaesthesia, particularly when sterilisation is performed, can be associated with significant morbidity in the form of pain, nausea and vomiting, dizziness and delayed mobilisation [3,4]. Consequently a number of these patients require admission to hospital for overnight stay.…”

Pathophysiology of itching in urticaria and atopic dermatitis

“…Kallikrein and papain, however, elicit a burning itch without the release of histamine from dermal mast cells (32,33). Prostaglandins (34)(35)(36)(37) and endorphins (38,39) induce no or only weak itching on their own, but potentiate histamine-induced itching, i.e. they may act as peripheral modulators of itching.…”