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Morphine Metabolite May Increase Pain Sensitivity

Subjects more sensitive to heat device after injection of morphine-6β-glucuronide

TUESDAY, May 26 (HealthDay News) -- Injections of the morphine metabolite morphine-6β-glucuronide (M6G) -- a potent analgesic in humans -- may also cause hyperalgesia, according to research published in the June issue of Anesthesiology.

Eveline L. van Dorp, M.D., of the Leiden University Medical Center in the Netherlands, and colleagues analyzed data from 40 adult volunteers, who were randomly assigned to receive intravenous injections of M6G or placebo; in each group, subjects had either an intravenous background infusion of naloxone or saline. Participants were exposed to heat pain from a thermal device. The researchers also report on mouse studies involving nociception after exposure to M6G.

In humans, a single injection of M6G was associated with increased pain sensitivity for at least six hours, the researchers discovered. The sensitivity was independent of the naloxone infusion. In mice, acute M6G injection caused analgesia in those implanted with placebo pellets, but hyperalgesia in mice given naltrexone pellets. Continuous infusion produced hyperalgesia in both types of mice, the authors note.

"Hyperalgesic effects of M6G in triple opioid receptor knockout mice clearly indicate that mechanisms apart from opioid receptors play a key role in this clinical phenomenon. Since morphine metabolites play indeed an important role for its effects and morphine continues to be the basis of the therapy of severe pain, detailed knowledge about the complete pharmacodynamic effects is a prerequisite to optimize pain therapy," writes the author of an accompanying editorial.

Paion AG donated M6G for the human study.

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