Cell Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Human Molecular Genetics, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University, Poznan, Poland.
Neurotox Res. 2020 Aug;38(2):385-397. doi: 10.1007/s12640-020-00214-z. Epub 2020 May 6.
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.
曲马多是一种可待因的人工合成类似物，常被开处方用于治疗轻度至中度疼痛。它有许多副作用，包括情绪不稳定和焦虑。在这项研究中，我们专注于慢性暴露于曲马多下前额叶皮层的结构和功能变化。在细胞水平上，PC12 细胞中 ROS 和膜联蛋白 V 的含量在接触曲马多后明显增加（浓度为 600μM ，持续 48 小时）。为此，大鼠每日用 50mg/kg 的曲马多处理 3 周。我们的研究结果表明，曲马多通过诱导凋亡标志物（如 Caspase 3 和 8）、促炎标志物和 GDNF 的下调，引发萎缩和细胞凋亡。此外，它还会引发小胶质细胞和星形胶质细胞的激活以及前额叶皮层中的神经元死亡。行为障碍和认知障碍也是曲马多的其他副作用。总的来说，我们的结果表明曲马多诱导的前额叶皮层神经退行性变主要是通过神经炎症反应的激活。
