Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School, Gwangju, Korea.
Korean J Pain. 2010 Sep;23(3):179-85. doi: 10.3344/kjp.2010.23.3.179. Epub 2010 Aug 26.
Vincristine-induced peripheral neuropathy is a major dose limiting side effect and thus effective therapeutic strategy is required. In this study, we investigated the antinociceptive effect of memantine and morphine on a vincristine-induced peripheral neuropathy model in rats.
Male Sprague-Dawley rats weighing 220-240 g were used in all experiments. Rats subsequently received daily intraperitoneal injections of either vincristine sulfate (0.1 ml/kg/day) or saline (0.1 ml/kg/day) over 12 days, immediately following behavioral testing. For assessment of mechanical allodynia, mechanical stimuli using von Frey filament was applied to the paw to measure withdrawal threshold. The effects of N-methyl-D-aspartate receptors antagonist (memantine; 2.5, 5, 10 mg/kg intraperitoneal), opioid agonist (morphine; 2.5, 5, 10 mg/kg intraperitoneal) and vehicle (saline) on vicristine-induced neuropathy were evaluated.
Mechanical allodynia developed over the course of ten daily injections of vincristine relative to groups receiving saline at the same time. Morphine abolished the reduction in paw withdrawal threshold compared to vehicle and produced dose-responsiveness. Only the highest dose of memantine (10 mg/kg) was able to increase paw withdrawal threshold compared to vehicle.
Systemic morphine and memantine have an antinociceptive effect on the vincristine-induced peripheral neuropathy model in rats. These results suggest morphine and memantine may be an alternative approach for the treatment of vincristine-induced peripheral neuropathic pain.
长春新碱诱导的周围神经病变是一种主要的剂量限制副作用，因此需要有效的治疗策略。在这项研究中，我们研究了美金刚和吗啡对长春新碱诱导的周围神经病模型大鼠的镇痛作用。
所有实验均使用体重为 220-240 g 的雄性 Sprague-Dawley 大鼠。大鼠随后在行为测试后每天接受长春新碱硫酸盐（0.1 ml/kg/天）或生理盐水（0.1 ml/kg/天）的腹腔内注射，共 12 天。为评估机械性痛觉过敏，使用 von Frey 细丝对足部施加机械刺激，以测量撤回阈值。评估 N-甲基-D-天冬氨酸受体拮抗剂（美金刚；2.5、5、10 mg/kg 腹腔内）、阿片类激动剂（吗啡；2.5、5、10 mg/kg 腹腔内）和载体（生理盐水）对长春新碱诱导的周围神经病的影响。
与同时接受生理盐水的组相比，长春新碱连续 10 天注射后出现机械性痛觉过敏。吗啡与载体相比，可消除足撤回阈值的降低，并产生剂量反应性。只有美金刚的最高剂量（10 mg/kg）可与载体相比增加足撤回阈值。
系统给予吗啡和美金刚对长春新碱诱导的周围神经病模型大鼠具有镇痛作用。这些结果表明，吗啡和美金刚可能是治疗长春新碱诱导的周围神经病理性疼痛的一种替代方法。
