Unraveling the Hippocampal Molecular and Cellular Alterations behind Tramadol and Tapentadol Neurobehavioral Toxicity

Data de publicação: 01/06/2024

Autores da FMUP

• Susana Isabel Ferreira Da Silva De Sá

  Autor

• Ricardo Jorge Dinis Oliveira

  Autor

Participantes de fora da FMUP

• Soares-Cardoso, Cristiana
• Leal, Sandra
• Dantas-Barros, Rita
• Faria, Juliana
• Barbosa, Joana

Unidades de investigação

• Biomedicina

• Ciências da Saúde Pública e Forenses, e Educação Médica

• Laboratório Associado RISE- Rede de Investigação em Saúde

  

  Investigador

  Fernando Carlos De Landér Schmitt

• RISE-Health

  

  Investigador

  Fernando Carlos De Landér Schmitt

Abstract

Tramadol and tapentadol are chemically related opioids prescribed for the analgesia of moderate to severe pain. Although safer than classical opioids, they are associated with neurotoxicity and behavioral dysfunction, which arise as a concern, considering their central action and growing misuse and abuse. The hippocampal formation is known to participate in memory and learning processes and has been documented to contribute to opioid dependence. Accordingly, the present study assessed molecular and cellular alterations in the hippocampal formation of Wistar rats intraperitoneally administered with 50 mg/kg tramadol or tapentadol for eight alternate days. Alterations were found in serum hydrogen peroxide, cysteine, homocysteine, and dopamine concentrations upon exposure to one or both opioids, as well as in hippocampal 8-hydroxydeoxyguanosine and gene expression levels of a panel of neurotoxicity, neuroinflammation, and neuromodulation biomarkers, assessed through quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemical analysis of hippocampal formation sections showed increased glial fibrillary acidic protein (GFAP) and decreased cluster of differentiation 11b (CD11b) protein expression, suggesting opioid-induced astrogliosis and microgliosis. Collectively, the results emphasize the hippocampal neuromodulator effects of tramadol and tapentadol, with potential behavioral implications, underlining the need to prescribe and use both opioids cautiously.

Keywords

• tramadol; tapentadol; prescription opioids; neurobehavioral toxicity; oxidative stress; neuroinflammation; neuromodulation; hippocampal formation; abuse; misuse