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BMC Cancer ; 21(1): 1128, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34670518

RESUMO

BACKGROUND: Clinically, the coadministration of opioids to enhance antinociception and decrease tolerance has attracted increasing research attention. We investigated the effects of dezocine, a mu- and kappa-opioid receptor agonist/antagonist, on morphine tolerance and explored the involvement of opioid receptor expression in a rat model of bone cancer pain. METHODS: Thermal nociceptive thresholds were measured after the subcutaneous injection of morphine (10 mg/kg) alone or combined with dezocine (10 or 1 mg/kg) for 7 consecutive days. Real-time PCR and western blot analysis were used to examine opioid receptor expression in the periaqueductal gray (PAG) and spinal cord. RESULTS: The analgesic effect was significantly decreased after 4 days of morphine administration. We observed that low-dose dezocine significantly attenuated morphine tolerance without reducing the analgesic effect of morphine. Low-dose dezocine coadministration significantly reversed the downregulated expression of mu (MOR) and delta (DOR) opioid receptors in the PAG and the upregulated expression of kappa (KOR) and DOR in the spinal cord induced by morphine. Moreover, low-dose dezocine coadministered with morphine significantly inhibited KOR expression in both the PAG and spinal cord. CONCLUSIONS: The combination of low-dose dezocine with morphine may prevent or delay the development of morphine tolerance in a rat model of bone cancer pain. The regulation of opioid receptor expression in the PAG and spinal cord may be part of the mechanism.


Assuntos
Analgésicos Opioides/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Dor do Câncer/tratamento farmacológico , Tolerância a Medicamentos , Morfina/farmacologia , Receptores Opioides/efeitos dos fármacos , Tetra-Hidronaftalenos/farmacologia , Analgésicos Opioides/administração & dosagem , Animais , Neoplasias Ósseas/complicações , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Dor do Câncer/metabolismo , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Interações Medicamentosas , Quimioterapia Combinada/métodos , Feminino , Temperatura Alta , Hiperalgesia/fisiopatologia , Morfina/administração & dosagem , Medição da Dor/efeitos dos fármacos , Limiar da Dor , Substância Cinzenta Periaquedutal/metabolismo , Ratos , Ratos Wistar , Receptores Opioides/metabolismo , Receptores Opioides delta/metabolismo , Receptores Opioides kappa/efeitos dos fármacos , Receptores Opioides kappa/metabolismo , Receptores Opioides mu/metabolismo , Medula Espinal/metabolismo , Tetra-Hidronaftalenos/administração & dosagem , Regulação para Cima/efeitos dos fármacos
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