Does Tramadol Exposure Have Unfavorable Effects on Hippocampus? A Review Study

Background: Tramadol, one of the most common opioid pain relievers, acts upon the µ-receptor in the central nervous system (CNS) to alleviate pain associated with various situations like postoperative pain, arthritis, and muscular pain. Additionally, it has been utilized to address depression and anxiety disorders. Extensive research has shown that tramadol can potentially inflict irreversible harm on different regions of the CNS, including the cerebrum, cerebellum, amygdala, and, notably, the hippocampal formation. However, the precise mechanism behind these effects remains unclear. Within this study, we conducted a comprehensive examination of the impacts of tramadol on the CNS, specifically focusing on hippocampal formation. Methods: In this study, we collected relevant articles published between 2000 and 2022 by conducting searches using specific keywords, including tramadol, tramadol hydrochloride, central nervous system, hippocampus, and hippocampal formation, in various databases. Findings: The results of this study proposed several processes by which tramadol may impact the CNS, including the induction of apoptosis, autophagy, excessive production of free radicals, and dysfunction of cellular organelles. These processes ultimately lead to disturbances in neural cell function, particularly within the hippocampus. Furthermore, it is revealed that tramadol administration led to a significant decrease in the neural cell count and the volume of various regions within the brain and spinal cord. Conclusion: Consequently, neuropsychological impairments, such as memory formation, attention deficits, and cognitive impairment, may happen. This finding highlights the potential impacts of tramadol on neural structures and warrants further investigation.