Joharchi Khojasteh, Jorjani Masoumeh
Neuroscience Research Center & Department of Pharmacology, Faculty of Medicine, Shaheed Beheshti Medical University, Tehran, Iran.
Eur J Pharmacol. 2007 Sep 10;570(1-3):66-71. doi: 10.1016/j.ejphar.2007.05.026. Epub 2007 Jun 5.
Several neuroendocrine complications including diabetes change the morphine antinociception and the development of tolerance to the drug. Morphine antinociception was reduced significantly in morphine tolerant diabetic rats compared to the non-diabetic animals. The exact mechanism of this effect is not known. This study was performed to determine the role of nitric oxide (NO) on morphine tolerance in diabetic state. Nociceptive responses in alloxan-induced diabetic morphine tolerated rats were measured by the hot-plate test. The urinary nitric oxide level was measured spectrophotometrically with Griess reagent. For the conversion of nitrate to nitrite, vanadium chloride was used. The results showed that experimental diabetes increased morphine analgesia. Conversely, degree of tolerance to morphine was diminished in diabetic state. The urinary nitrite content in diabetic morphine tolerated rats was higher than non-diabetic groups. L-arginine significantly increased the NO production in diabetic morphine tolerated animals, whereas aminoguanidine decreased it. Appropriately, L-arginine increased the latency time of reaction to noxious stimuli in diabetic compared to non-diabetic rats. L-arginine-treated animals also showed more tolerance to morphine analgesia. As expected, aminoguanidine deducted the level of morphine tolerance in diabetic animals. It is suggested that NO has a modulatory role in the effects of diabetes on morphine analgesia and tolerance.
包括糖尿病在内的几种神经内分泌并发症会改变吗啡的抗伤害感受作用以及对该药物耐受性的发展。与非糖尿病动物相比，吗啡耐受的糖尿病大鼠的吗啡抗伤害感受作用显著降低。这种效应的确切机制尚不清楚。本研究旨在确定一氧化氮（NO）在糖尿病状态下对吗啡耐受性的作用。通过热板试验测量四氧嘧啶诱导的糖尿病吗啡耐受大鼠的伤害性反应。用格里斯试剂通过分光光度法测量尿中一氧化氮水平。为了将硝酸盐转化为亚硝酸盐，使用了氯化钒。结果表明，实验性糖尿病增强了吗啡镇痛作用。相反，在糖尿病状态下对吗啡的耐受程度降低。糖尿病吗啡耐受大鼠的尿中亚硝酸盐含量高于非糖尿病组。L-精氨酸显著增加糖尿病吗啡耐受动物的NO生成，而氨基胍则降低其生成。相应地，与非糖尿病大鼠相比，L-精氨酸增加了糖尿病大鼠对有害刺激反应的潜伏期。L-精氨酸处理的动物对吗啡镇痛也表现出更高的耐受性。正如预期的那样，氨基胍降低了糖尿病动物的吗啡耐受水平。提示NO在糖尿病对吗啡镇痛和耐受性的影响中具有调节作用。
