Morphine-6beta-glucuronide rapidly increases pain sensitivity independently of opioid receptor activity in mice and humans.
Anesthesiology
; 110(6): 1356-63, 2009 Jun.
Article
em En
| MEDLINE
| ID: mdl-19461298
ABSTRACT
BACKGROUND:
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.METHODS:
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.RESULTS:
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.CONCLUSIONS:
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores Opioides
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Hiperalgesia
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Derivados da Morfina
Tipo de estudo:
Clinical_trials
/
Diagnostic_studies
Limite:
Adolescent
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Adult
/
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Anesthesiology
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Holanda