Attempts to elucidate the pathophysiology of pruritus have implicated a number of chemicals that have the ability to trigger itching, the most important being histamine.1 Among other itch-inducing agents are the morphine alkaloids, which are of special interest due to their contrary effects on the sensations of pain and itching; they relieve one while exacerbating the other. The activation of itch by morphine is thought to be due to direct histamine release from tissue mast cells.2 However, antihistamines seldom completely block the pruritus secondary to morphine administration and they sometimes provide only a little relief. Furthermore, intracisternal or intramedullary injection of morphine in different animals results in a scratch response that suggests another reason for morphine's effects.3,4
The central itch-provoking effect of morphine is intriguing in light of recent evidence of the existence of central opiate receptors and naturally occurring peptides with opiate activity in the mammalian
Bernstein JE, Swift R. Relief of Intractable Pruritus With Naloxone. Arch Dermatol. 1979;115(11):1366–1367. doi:https://doi.org/10.1001/archderm.1979.04010110058029
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