Science translational medicine
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Morphine-induced itch is a very common and debilitating side effect that occurs in laboring women who receive epidural analgesia and in patients who receive spinal morphine for relief of perioperative pain. Although antihistamines are still widely prescribed for the treatment of morphine-induced itch, their use is controversial because the cellular basis for morphine-induced itch remains unclear. ⋯ Agonism of the kappa-opioid receptor alleviated morphine-induced itch in mice and nonhuman primates. Thus, our findings not only reveal that morphine causes itch through a mechanism of disinhibition but also challenge the long-standing use of antihistamines, thereby informing the treatment of millions worldwide.