PDF(Pubmed)
Abstract：
Tramadol and tapentadol are chemically related opioids prescribed for the analgesia of moderate to severe pain. Although safer than classical opioids, they are associated with neurotoxicity and behavioral dysfunction, which arise as a concern, considering their central action and growing misuse and abuse. The hippocampal formation is known to participate in memory and learning processes and has been documented to contribute to opioid dependence. Accordingly, the present study assessed molecular and cellular alterations in the hippocampal formation of Wistar rats intraperitoneally administered with 50 mg/kg tramadol or tapentadol for eight alternate days. Alterations were found in serum hydrogen peroxide, cysteine, homocysteine, and dopamine concentrations upon exposure to one or both opioids, as well as in hippocampal 8-hydroxydeoxyguanosine and gene expression levels of a panel of neurotoxicity, neuroinflammation, and neuromodulation biomarkers, assessed through quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemical analysis of hippocampal formation sections showed increased glial fibrillary acidic protein (GFAP) and decreased cluster of differentiation 11b (CD11b) protein expression, suggesting opioid-induced astrogliosis and microgliosis. Collectively, the results emphasize the hippocampal neuromodulator effects of tramadol and tapentadol, with potential behavioral implications, underlining the need to prescribe and use both opioids cautiously.
摘要：
曲马多和他喷他多是化学相关的阿片类药物，用于中度至重度疼痛的镇痛。虽然比经典阿片类药物更安全，它们与神经毒性和行为功能障碍有关，这是一个令人担忧的问题，考虑到他们的中心行动和越来越多的误用和滥用。已知海马结构参与记忆和学习过程，并已被证明有助于阿片类药物依赖。因此，本研究评估了Wistar大鼠腹腔注射50mg/kg曲马多或他他他他多间隔8天的海马结构的分子和细胞变化.在血清过氧化氢中发现了变化，半胱氨酸,同型半胱氨酸,暴露于一种或两种阿片类药物后的多巴胺浓度，以及在海马8-羟基脱氧鸟苷和一组神经毒性的基因表达水平，神经炎症，和神经调节生物标志物，通过定量实时聚合酶链反应（qRT-PCR）评估。免疫组织化学分析海马结构切片显示胶质纤维酸性蛋白（GFAP）增加，分化簇11b（CD11b）蛋白表达减少，提示阿片类药物诱导的星形胶质细胞增生和小胶质细胞增生。总的来说，结果强调了曲马多和他喷他多的海马神经调质作用，具有潜在的行为影响，强调开处方和谨慎使用两种阿片类药物的必要性。
