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Chronic Exposure to Tramadol Induces Neurodegeneration in the Cerebellum of Adult Male Rats

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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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Acknowledgements

This article has been extracted from the Ph.D. thesis written by Ms. Samira Ezi. We also thank Netsaai group for providing us computational infrastructure.

Funding

We received funding from Hearing Disorders Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran (Registration No: 23846). The present article is financially supported by School of Medicine, Shahid Beheshti University of Medical Sciences.

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Author notes

  1. Samira Ezi and Mahdi Eskandarian Boroujeni contributed equally to this work.

Authors and Affiliations

  1. Hearing Disorders Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Iran University of Medical Sciences, Tehran, Iran

    Samira Ezi & Abbas Aliaghaei

  2. Department of Cell Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Samira Ezi, Aysan Khatmi, Mohammad-Amin Abdollahifar, Fakhroddin Aghajanpour, Reza Soltani, Seyed Hamidreza Mirbehbahani, Abbas Aliaghaei & Reza Mastery Farahani

  3. Department of Human Molecular Genetics, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University, Poznan, Poland

    Mahdi Eskandarian Boroujeni

  4. Student Research Committee, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Kimia Vakili & Mobina Fathi

  5. Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Fariba Khodagholi

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  1. Samira Ezi
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Ezi, S., Boroujeni, M.E., Khatmi, A. et al. Chronic Exposure to Tramadol Induces Neurodegeneration in the Cerebellum of Adult Male Rats. Neurotox Res 39, 1134–1147 (2021). https://doi.org/10.1007/s12640-021-00354-w

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