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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Adolescent, Adult, Animals, Dizocilpine Maleate, Female, Humans, Hyperalgesia, Male, Mice, Mice, Knockout, Morphine Derivatives, Naloxone, Naltrexone, Narcotic Antagonists, Pain Measurement, Reaction Time, Receptors, N-Methyl-D-Aspartate, Receptors, Opioid, Receptors, Opioid, delta, Receptors, Opioid, kappa, Receptors, Opioid, mu, Young Adult.
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Does morphine-6beta-glucuronide rapidly increase pain sensitivity independently of opioid receptor activity in mice and humans? Context: Previous data indicate that morphine-6beta-glucuronide (M6G), a morphine metabolite with analgesic properties, can paradoxically increase pain sensitivity in mice and humans. The authors tested mice and humans for M6G hyperalgesia and assessed the contribution of N-methyl-D-aspartate receptor activity in mice. Nociception after acute injection (10 mg/kg) and chronic infusion (1.6 mg/kg per 24 h) of M6G or saline was assayed using the tail-withdrawal test in CD-1 mice implanted with pellets containing the opioid antagonist naltrexone or placebo and in knockout mice lacking mu-, kappa-, and delta-opioid receptors and their B6129F(1) controls. In volunteers, responses to heat pain were tested after a M6G (0.4 mg/kg) injection in the presence of a continuous high naloxone (0.04-mg/kg bolus followed by 0.04 mg/kg per hour) or saline background infusion. Acute M6G injection evoked analgesia in CD-1 mice implanted with placebo pellets and B6129F(1) control mice, whereas it caused hyperalgesia in CD-1 mice treated concurrently with naltrexone and in knockout mice. Continuous M6G infusion produced hyperalgesia within 24 h, lasting for a minimum of 6 days, in both placebo- and naltrexone-pelleted mice. The N-methyl-D-aspartate receptor antagonist MK-801 (0.05 mg/kg) blocked and reversed hyperalgesia after the acute injection and continuous infusion of M6G, respectively. In humans, M6G increased heat pain sensitivity for at least 6 h independently of simultaneous naloxone infusion.
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These data indicate that M6G causes hyperalgesia independent of previous or concurrent opioid receptor activity or analgesia. In mice, a causal role for the N-methyl-D-aspartate receptor is also indicated. Final Decision: yes