Tramadol effects on the nucleus accumbens – insights from in vitro and in vivo studies

• Autor(es): Pinho , Sara ; Dinis-Oliveira , Ricardo Jorge ; Faria , Juliana ; Barbosa, Joana
• Data: 2024
• Origem: Scientific Letters
• Assunto(s): Poster
• Tipo de Documento: Artigo científico
• Idioma: Inglês

Descrição

Background: Tramadol is mainly used for the treatment of moderate to severe pain. It synergistically combines two distinct mechanisms of action, being a selective agonist for mu-opioid receptors (MOR) and inhibiting serotonin and noradrenaline reuptake, which improves its analgesic and safety profile [1]. However, it is not devoid of neurobehavioral toxicity potential [2], whose molecular alterations are not fully clarified. Due to its primary role in reward, motivation and drug self-administration behaviors, the nucleus accumbens (NAC) is anticipated to participate in the mechanisms of tramadol addiction, dependence and toxicity. Objective: The aim of this review is to summarize the main neurotoxicity biomarkers and effects of tramadol exposure on the NAC. Methods: A bibliographic research of neurotoxicity biomarkers and findings concerning the NAC, upon exposure to tramadol, was performed on the National Library of Medicine (PubMed), with no temporal restrictions and considering in vitro and in vivo studies. Results: In vivo studies showed increased levels of MOR, p-CREB and deltaFosB in the NAC after acute and chronic exposure to tramadol (5 and 10 mg/kg) [3]. Even if apoptosis and inflammation are major NAC findings in in vivo studies, autophagy was also upregulated in in vitro studies with PC12 cells exposed to 50 mM tramadol [4]. In addition, it has been found that tramadol enhances dopamine levels in the NAC shell and that NAC cannabinoid receptor 1 (CB1R) is involved in tramadol reinforcing effect and reinstatement [5]. Conclusions: In conclusion, although tramadol controls pain more effectively and with fewer adverse events than classical opioids, its neurotoxic potential is of particular concern. The nucleus accumbens has a relevant contribution to such neurobehavioral toxicity, as shown by multiple alterations in important cell death, inflammation and related signaling pathways. A personalized and cautious tramadol prescription is thus mandatory.