Opioid neurotoxicity: Comparison of morphine and tramadol in an experimental rat model
Opioid neurotoxicity: Comparison of morphine and tramadol in an experimental rat model
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DOI：
10.1080/00207450490461314
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发表时间：
2004-08-01
影响因子：
2.2
通讯作者：
Oral, U
中科院分区：
文献类型：
--
作者：
Atici, S;Cinel, L;Oral, U
本研究探讨了长期使用吗啡和/或曲马多逐渐增加剂量引起的大鼠脑组织病理学变化。选取雄性Wistar大鼠30只，体重180 ~ 220 g，分为3组。对照组（n = 10）腹腔注射生理盐水（1 ml/kg）作为安慰剂。吗啡组（n = 10）前10天腹腔注射吗啡，剂量为4 mg/kg/d， 11-20天剂量为8 mg/kg/d， 21-30天剂量为12 mg/kg/d。曲马多组（n = 10）在研究的第1、2、3个10天分别以20、40、80 mg/kg/天的剂量腹腔注射曲马多。所有大鼠于第30天斩首，取脑组织作组织学检查。在顶叶、额叶、颞叶、枕叶、内嗅、梨状和海马CA1、CA2、CA3区，研究了红色神经元的存在和数量，红色神经元是细胞凋亡的组织学标志。吗啡组和曲马多组有红色神经元，对照组无。吗啡组和曲马多组红色神经元总数差异无统计学意义，但曲马多组颞、枕区红色神经元数量显著高于吗啡组（p < 0.05）。综上所述，长期使用吗啡和/或曲马多增加剂量会导致大鼠脑中的红色神经元变性，这可能导致脑功能障碍。当阿片类药物使用铬时，应考虑这些发现。
Histopathologic changes in rat brain due to chronic use of morphine and/or tramadol in progressively increased doses were investigated in this study. Thirty male Wistar rats (180-220 g) were included and divided into three groups. Normal saline (I ml/kg) was given intraperitoneally as placebo in the control group (n = 10). Morphine group (n = 10) received morphine intraperitoneally at a dose of 4 mg/kg/day for the first 10 days, 8 mg/kg/day between 11-20 days, and 12 mg/kg/day between 21-30 days. The tramadol group (n = 10) received the drug intraperitoneally at doses of 20, 40, and 80 mg/kg/day in the first, second, and the third 10 days of the study, respectively. All rats were decapitated on the 30th day and the brain was removed intact for histology. The presence and the number of red neurons, which are a histologic marker of apoptosis, were investigated in the parietal, frontal, temporal, occipital, entorhinal, pyriform, and hippocampal CA1, CA2, CA3 regions. Red neurons were found in morphine and tramadol groups but not in the control group. The total number of red neurons was not different in morphine and tramadol groups, but the numbers of red neurons were significantly higher in the temporal and occipital regions in tramadol group as compared with the morphine group (p < .05). In conclusion, chronic use of morphine and/or tramadol in increasing doses is found to cause red neuron degeneration in the rat brain, which probably contributes to cerebral dysfunction. These findings should be taken into consideration when chrome use of opioids is indicated.