Activation of spinal Extacellular Signal-Regulated Kinases and c-jun N-terminal kinase signaling pathways contributes to morphine-induced acute and chronic hyperalgesia in mice.
J Cell Biochem
; 120(9): 15045-15056, 2019 09.
Article
em En
| MEDLINE
| ID: mdl-31016764
ABSTRACT
BACKGROUND:
This study investigated the activation of mitogen-activated protein kinases in the spinal dorsal horn to explore the mechanisms underlying morphine-induced acute and chronic hyperalgesia in mice.METHODS:
Male adult mice were given a single subcutaneous injection (SC) of morphine (1 µg/kg) or twice-daily administration of morphine (10 mg/kg/day) for 8 days. Thermal hyperalgesia and mechanical allodynia were assessed using the radiant heat and von Frey filament test. Levels of phospho (p)-extracellular signal-regulated kinases (p-ERK), p-c-Jun N-terminal kinase (p-JNK), p-p38, p-PKCγ, N-methyl-d-aspartate receptor (NMDAr), and c-Fos protein in the spinal dorsal horn were examined by Western blot assays.RESULTS:
A single ultra-low dose or repeated administration of morphine induced hyperalgesia in mice and caused a significant increase in the levels of p-ERK and p-JNK, but not p-p38, in the spinal dorsal horn. The level of c-Fos protein was significantly elevated following administration of morphine. The protein levels of p-PKCγ and NMDAr subunits (NR2B and NR2A) were also altered. Pretreatment with the NMDAr antagonist MK-801 or the protein kinase C (PKC) inhibitor calphostin C (CC) suppressed the morphine-induced increase in p-ERK, p-JNK, and c-Fos. Administration of MK-801 and CC also relieved morphine-induced hyperalgesia.CONCLUSION:
These findings suggest that activation of the spinal ERK and JNK signaling pathways contribute to morphine-induced acute and chronic hyperalgesia in mice.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
MAP Quinases Reguladas por Sinal Extracelular
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Proteínas Quinases JNK Ativadas por Mitógeno
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Corno Dorsal da Medula Espinal
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Hiperalgesia
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Analgésicos Opioides
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Morfina
Limite:
Animals
Idioma:
En
Revista:
J Cell Biochem
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China