Chronic oxycodone induces axonal degeneration in rat brain.
BMC Neurosci
; 19(1): 15, 2018 03 23.
Article
em En
| MEDLINE
| ID: mdl-29571287
ABSTRACT
BACKGROUND:
Chronic opioid therapy for non-malignant pain conditions has significantly increased over the last 15 years. Recently, the correlation between opioid analgesics and alternations in brain structure, such as leukoencephalopathy, axon demyelination, and white matter lesions, has been demonstrated in patients with a history of long-term use of prescription opioids. The exact mechanisms underlying the neurotoxic effect of opioids on the central nervous system are still not fully understood. We investigated the effect of chronic opioids using an animal model in which female rats were orally gavaged with 15 mg/kg of oxycodone every 24 h for 30 days. In addition we tested oxycodone, morphine and DAMGO in breast adenocarcinoma MCF7 cells, which are known to express the µ-opioid receptor.RESULTS:
We observed several changes in the white matter of animals treated with oxycodone deformation of axonal tracks, reduction in size of axonal fascicles, loss of myelin basic protein and accumulation of amyloid precursor protein beta (ß-APP), suggesting axonal damages by chronic oxycodone. Moreover, we demonstrated activation of pro-apoptotic machinery amid suppression of anti-apoptotic signaling in axonal tracks that correlated with activation of biomarkers of the integrated stress response (ISR) in these structures after oxycodone exposure. Using MCF7 cells, we observed induction of the ISR and pro-apoptotic signaling after opioid treatment. We showed that the ISR inhibitor, ISRIB, suppresses opioid-induced Bax and CHOP expression in MCF7 cells.CONCLUSIONS:
Altogether, our data suggest that chronic opioid administration may cause neuronal degeneration by activation of the integrated stress response leading to induction of apoptotic signaling in neurons and also by promoting demyelination in CNS.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oxicodona
/
Receptores Opioides mu
/
Analgésicos Opioides
/
Morfina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
BMC Neurosci
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos