Morphine-3-glucuronide causes antinociceptive cross-tolerance to morphine and increases spinal substance P expression.
Eur J Pharmacol
; 875: 173021, 2020 May 15.
Article
em En
| MEDLINE
| ID: mdl-32112778
ABSTRACT
Morphine-3-glucuronide (M3G), the main metabolite of morphine, has been implicated in the development of tolerance and of opioid-induced hyperalgesia, both limiting the analgesic use of morphine. We evaluated the acute and chronic effects of M3G and morphine as well as development of antinociceptive cross-tolerance between morphine and M3G after intrathecal administration and assessed the expression of pain-associated neurotransmitter substance P in the spinal cord. Sprague-Dawley rats received intrathecal M3G or morphine twice daily for 6 days. Nociception and tactile allodynia were measured with von Frey filaments after acute and chronic treatments. Substance P levels in the dorsal horn of the spinal cord were determined by immunohistochemistry after 4-day treatments. Acute morphine caused antinociception as expected, whereas acute M3G caused tactile allodynia, as did both chronic M3G and morphine. Chronic M3G also induced antinociceptive cross-tolerance to morphine. M3G and morphine increased substance P levels similarly in the nociceptive laminae of the spinal cord. This study shows that chronic intrathecal M3G sensitises animals to mechanical stimulation and elevates substance P levels in the nociceptive laminae of the spinal cord. Chronic M3G also induces antinociceptive cross-tolerance to morphine. Thus, chronic M3G exposure might contribute to morphine-induced tolerance and opioid-induced hyperalgesia.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Nociceptividade
/
Hiperalgesia
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Estimulantes do Sistema Nervoso Central
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Morfina
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Derivados da Morfina
Tipo de estudo:
Diagnostic_studies
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Etiology_studies
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Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article