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Findings from Leiden University in anesthesiology reported

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"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," wrote E.L.A. Vandorp and colleagues, Leiden University.

The researchers concluded: "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."

Vandorp and colleagues published their study in Anesthesiology (Morphine-6 beta-glucuronide Rapidly increases Pain Sensitivity Independently of Opioid Receptor Activity in Mice and Humans. Anesthesiology, 2009;110(6):1356-1363).

For additional information, contact A. Dahan, Leiden University, Medical Center, Dept. of Anesthesiology, P5-Q, POB 9600, NL-2300 RC Leiden, Netherlands.

Publisher contact information for the journal Anesthesiology is: Lippincott Williams & Wilkins, 530 Walnut St., Philadelphia, PA 19106-3621, USA.

Keywords: Netherlands, Life Sciences, Naltrexone, Drugs, Therapy, Treatment, Hyperalgesia, Naloxone Hydrochloride, Pharmaceuticals, Morphine, Analgesic, Narcotic, Opiate Agonist, Alcohol Antagonist, Anticraving, Depressant, Opiate Antagonist, Neurology, Opioid Receptors, Pain Medicine, Analgesia, Anesthesiology, Leiden University.

This article was prepared by Pain & Central Nervous System Week editors from staff and other reports. Copyright 2009, Pain & Central Nervous System Week via NewsRx.com.