ArticleNeurotoxicity research2020
Tramadol: a Potential Neurotoxic Agent Affecting Prefrontal Cortices in Adult Male Rats and PC-12 Cell Line.
Article in Neurotoxicity research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 28 citations in OpenAlex.
- Tramadol induces hormonal imbalance, histopathology, and altered ovarian gene expression in mice.Clinical and experimental reproductive medicine · 2026Article
- Potent Ameliorative Effects of Rosmarinic Acid on Tramadol-Induced Neurotoxicity in the Brain and Hippocampus; by Suppressing Oxidative stress, Apoptosis, ER stress, and Regulating Cognitive Functions.Molecular neurobiology · 2025Article
- Tramadol use and incident dementia in older adults with musculoskeletal pain: a population-based retrospective cohort study.Scientific reports · 2024Article
- Does Tramadol Exposure Have Unfavorable Effects on Hippocampus? A Review Study.Addiction & health · 2024Review
- Minocycline Acts as a Neuroprotective Agent Against Tramadol-Induced Neurodegeneration: Behavioral and Molecular Evidence.International journal of preventive medicine · 2024Article
- Role of apoptosis and autophagy in mediating tramadol-induced neurodegeneration in the rat hippocampus.Molecular biology reports · 2023Article
- Plasma Brain-Derived Neurotrophic Factor and Opioid Therapy: Results of Pilot Cross-Sectional Study.Clinical medicine & research · 2022Article
- Comparative Study of the Neurotoxic Effects of Pregabalin Versus Tramadol in Rats.Neurotoxicity research · 2022Article
- Spectral Power Density analysis of the resting-state as a marker of the central effects of opioid use in fibromyalgia.Scientific reports · 2021Observational
- Chronic Exposure to Tramadol Induces Neurodegeneration in the Cerebellum of Adult Male Rats.Neurotoxicity research · 2021Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tramadol is a synthetic analogue of codeine that is often prescribed for the treatment of mild to moderate pains. It has a number of side effects including emotional instability and anxiety. In this study, we focus on the structural and functional changes of prefrontal cortex under chronic exposure to tramadol. At the cellular level, the amounts of ROS and annexin V in PC12 cells were evidently increased upon exposure to tramadol (at a concentration of 600 μM for 48 h). To this end, the rats were daily treated with tramadol at doses of 50 mg/kg for 3 weeks. Our findings reveal that tramadol provokes atrophy and apoptosis by the induction of apoptotic markers such as Caspase 3 and 8, pro-inflammatory markers, and downregulation of GDNF. Moreover, it triggers microgliosis and astrogliosis along with neuronal death in the prefrontal cortex. Behavioral disturbance and cognitive impairment are other side effects of tramadol. Overall, our results indicate tramadol-induced neurodegeneration in the prefrontal cortex mainly through activation of neuroinflammatory response.
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