ArticleNeurotoxicity research2021
Chronic Exposure to Tramadol Induces Neurodegeneration in the Cerebellum of Adult Male Rats.
Article in Neurotoxicity research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 24 citations in OpenAlex.
- Cell-type specific impact of opioid use disorder and HIV on the human forebrain and cerebellum.bioRxiv : the preprint server for biology · 2026Article
- Astrocytes and Astrocyte-Derived Extracellular Conduits in Opiate-Mediated Neurological Disorders.Cells · 2025Review
- Neurotoxic Effects of Tramadol Administration on the Cerebellar and Cerebral Cortices of Adult Male Wistar Rats.Cureus · 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
- Unraveling the Hippocampal Molecular and Cellular Alterations behind Tramadol and Tapentadol Neurobehavioral Toxicity.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Evaluation of histological and ultrastructural changes provoked by prenatal tramadol on postnatal cortical cerebellar neuronal development in rats: possible implication of Ki67, GFAP and MicroRNA-7/P53 signalling trajectories.Journal of molecular histology · 2024Article
- Tramadol induces apoptosis, inflammation, and oxidative stress in rat choroid plexus.Metabolic brain disease · 2023Article
- Role of apoptosis and autophagy in mediating tramadol-induced neurodegeneration in the rat hippocampus.Molecular biology reports · 2023Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tramadol is a centrally acting synthetic opioid analgesic and SNRI (serotonin/norepinephrine reuptake-inhibitor) that structurally resembles codeine and morphine. Given the tramadol neurotoxic effect and the body of studies on the effect of tramadol on the cerebellum, this study aims to provide deeper insights into molecular and histological alterations in the cerebellar cortex related to tramadol administration. In this study, twenty-four adult male albino rats were randomly and equally divided into two groups: control and tramadol groups. The tramadol group received 50 mg/kg of tramadol daily for 3 weeks via oral gavage. The functional and structural change of the cerebellum under chronic exposure of tramadol were measured. Our data revealed that treating rats with tramadol not only lead to cerebellum atrophy but also resulted in the actuation of microgliosis, neuroinflammatoin, and apoptotic biomarkers. Our results illustrated a significant drop in VEGF (vascular endothelial growth factor) level in the tramadol group. Additionally, tramadol impaired motor coordination and neuromuscular activity. We also identified several signaling cascades chiefly related to neurodegenerative disease and energy metabolism that considerably deregulated in the cerebellum of tramadol-treated rats. Overall, the outcomes of this study suggest that tramadol administration has a neurodegeneration effect on the cerebellar cortex via several pathways consisting of microgliosis, apoptosis, necroptosis, and neuroinflammatoin.
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