Evidence for Separate Involvement of Different μ-Opioid Receptor Subtypes in Itch and Analgesia Induced by Supraspinal Action of Opioids

The common adverse effect of centrally-injected μ-opioid receptor (μ-OR) agonists is pruritus. This study was conducted using mice to examine whether different subtypes of μ-OR would be responsible for pruritus and analgesia. Intracisternal injections of morphine and morphine-6β-glucronide (M6G), but not M3G, produced an antinociceptive effect. Morphine, but neither M6G nor M3G, induced facial scratching, a pruritus-related response. Facial scratching following morphine was not affected by the μ 1-OR antagonist naloxonazine at doses that inhibited the antinociceptive effects. The results suggest that different subtype and/or splice variants of μ-OR are separately involved in pruritus and antinociception of opioids. Keywords:: morphine, morphine-6β-glucronide, itch