NITROUS OXIDE AND ENDORPHINS

一氧化二氮被广泛用于临床，用于清醒镇静，也可用于 然而，手术麻醉的止痛作用机制是 仍然一无所知。其他调查人员报告说，亚硝酸盐 阿片受体阻滞剂拮抗氧化诱导的镇痛 纳洛酮，在初步调查中，我们发现接触到 75%一氧化二氮：25%氧气产生可逆性增加 人工合成的甲硫氨酸-脑啡肽(ME)样免疫反应 脑脊液采集自脑室脑池灌流， 麻醉大鼠。基于这些发现，我们假设亚硝酸盐 氧化物可以诱导神经元释放特定的阿片肽，这 药物作用可能与亚硝酸盐的镇痛作用有关。 氧化物。我们的具体目标是将这一假设提交给一组测试 旨在验证阿片类药物参与生理学研究的假设 或药理过程。这些测试将涉及1.对抗 纳洛酮，2.不被(+)-纳洛酮拮抗，3.交叉耐受 吗啡，4.脑啡肽代谢抑制剂的增强作用，以及5. 阿片肽的释放演示。这些测试将是 在行为模型中使用一氧化二氮诱导的镇痛和 一氧化二氮对大鼠脑灌流液ME样免疫反应的影响 麻醉清醒的大鼠中央灌流。我们的方法将 包括大鼠甩尾实验，大鼠热板实验， 脑室-脑池灌注、鞘内灌注、放射免疫测定 阿片类药物的高效液相色谱分离或分析 多肽。这项研究的长期目标是系统地 分析一氧化二氮的药物作用和影响，最终分析其他 全身麻醉药也是。这项研究的发现应该是 有助于我们了解和了解黄连的药理作用 一氧化二氮。

Nitrous oxide is widely used clinically for conscious sedation and also in surgical anesthesia, however, the mechanism of its analgesic action has remained unknow. Other investigators have reported that nitrous oxide-induced analgesia is antagonized by the opiate receptor blocker naloxone and, in preliminary investigations, we have found that exposure to 75% nitrous oxide: 25% oxygen produces a reversible increase in the methionine-enkephalin (ME)-like immunoreactivity in fractions of artificial cerebrospinal fluid collected from ventricular-cisternally-perfused, anesthetized rats. Based upon these findings, we hypothesize that nitrous oxide can induce neuronal release of specific opioid peptides and that this drug action might be associated with the analgesic effect of nitrous oxide. Our specific aim is to submit this hypothesis to testing by a set of postulates designed to verify an opiate involvement in a physiological or pharmacological process. These tests will involve 1. antagonism by naloxone, 2. non-antagonism by (+)-naloxone, 3. cross-tolerance with morphine, 4. potentiation by inhibitors of enkephalin metabolism, and 5. demonstration of release of opioid peptides. These tests will be conducted, using nitrous oxide-induced analgesia in behavioral models and nitrous oxide-induced changes in perfusate ME-like immunoreactivity in anesthetized and conscious centrally-perfused rats. Our methods will include the rat tail flick test, the rat hot plate test, ventricular-cisternal perfusion, intrathecal perfusion, radioimmunoassay and high performance liquid chromatography separation or assay of opioid peptides. The long-term objectives of this research are to systemically analyze the drug actions and effects of nitrous oxide and eventually other general anesthetic drugs as well. The findings of this research should contribute to our understanding and knowledge of the pharmacology of nitrous oxide.