Objective: The current study is designed to evaluate the possible neurotoxic effects of tramadol in Wistar rats.

Background: Parkinson’s disease (PD) is a chronic neurodegenerative disorder triggered by degeneration of dopaminergic neurons in substantia nigra pars compacta (SNpc), with the deficiency of dopamine responsible for motor abnormalities. Excessive neurodegeneration due to low antioxidant level, mitochondrial failure and neuroinflammation are the major pathological factors. Tramadol is a safe analgesic drug but its chronic utilization interferes with dopamine synthesis, release and inhibit various neurotransmitters responsible for Parkinson’s like symptoms.

Method: Rats were administrated intraperitoneal injection of tramadol 50 mg/kg daily for 28 days. Motor coordination activities were carried out by rotarod, narrow beam walk, open field and grip strength on the weekly basis. On the 29^th day, all animals were sacrificed and striatum homogenates were used for neuroinflammatory (tumor necrosis factor -α, interleukin-1β and interleukin-17), biochemical (lipid peroxidation, nitrite, glutathione, mitochondrial complex I, IV and Cyclic adenosine monophosphate), and neurotransmitters (dopamine, norepinephrine, serotonin, gamma-Aminobutyric Acid, glutamate) analysis.

Results: Rats administration with tramadol showed significantly induct motor deficits by decreased antioxidant levels (SOD, GSH, catalase), increased striatal proinflammatory cytokines level (TNF- α, IL-1β, IL-17) dysbalanced neurotransmitters (dopamine, norepinephrine, serotonin, gamma-Aminobutyric Acid, glutamate) and reduced mitochondrial complex activity (mitochondrial complex I, IV and cAMP).

Conclusion: The outcome of this research suggested that chronic tramadol administration produces impaired motor functions, increased oxidative stress, neuroinflammation, altered neurotransmitters level and produced PD like Symptoms in experimental Wistar rats.

References: 1. Mohamed HM, Mahmoud AM (2019) Chronic exposure to the opioid tramadol induces oxidative damage, inflammation and apoptosis, and alters cerebral monoamine neurotransmitters in rats. Biomed Pharmacother. 110:239-247. https://doi.org/10.1016/j.biopha.2018.11.141.
2. Oertel WH (2017) Recent advances in treating Parkinson’s disease. F1000Res. 6:1-14. https://doi.org/10.12688/f1000research.10100.1.
3. Raj K, Chawla P, Singh S (2019) Neurobehavioral Consequences Associated with Long Term Tramadol Utilization and Pathological Mechanisms. CNS & Neurological Disorders-Drug Targets (Formerly Current Drug Targets-CNS & Neurological Disorders) 18:758-768. https://doi.org/10.2174/1871527318666191112124435

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MDS Abstracts - https://www.mdsabstracts.org/abstract/tramadol-induces-neuroinflammation-mitochondrial-oxidative-stress-neurotransmitters-dysbalanced-and-produced-parkinsons-disease-like-symptoms-in-experimental-wistar-rats/