NITROUS OXIDE AND ENDOGENOUS OPIOID SYSTEMS

一氧化二氮和内源性阿片类药物系统

• 批准号: 3220392
• 负责人: RAYMOND MARK QUOCK
• 金额: $ 23.26万
• 依托单位: COLLEGE OF MEDICINE AT ROCKFORD
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-12-01 至 1993-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3220392
• 关键词: analgesics; blood chemistry; blood pressure; body temperature; brain metabolism; drug interactions; drug tolerance; halothane; high performance liquid chromatography; laboratory rat; microinjections; narcotic antagonists; neuropeptide receptor; neuropeptides; neuropharmacology; nitrous oxide; radioimmunoassay; spinal cord; stereotaxic techniques

Nitrous oxide is a gaseous pharmacological agent with a broad range of clinical applications in medicine and dentistry. Despite the use of nitrous oxide as a clinical analgesic agent, its mechanism of action remains somewhat nebulous. Recent research conducted in our laboratory and elsewhere implicates an interaction of subanesthetic concentrations of nitrous oxide with endogenous opioid systems. Based on various experimental findings, we hypothesize that nitrous oxide analgesia might result from drug-stimulated neuronal release of specific endogenous opioid peptides (EOPs) with subsequent activation of central analgesia-mediating opioid receptors. Over the past several years, research efforts in our laboratory have been devoted to further eluci- dation of this opioid connection in nitrous oxide analgesia. The objectives of this proposed research are to: (1) identify the subtype(s) and location(s) of central opioid receptors that mediate nitrous oxide analgesia; (2) quantify and identify the increased EOPs in artificial cerebrospinal fluid perfusate collected from both anesthetized and conscious, centrally perfused rats exposed to nitrous oxide; and (3) correlate the degree of nitrous oxide analgesia with changes in regional brain and spinal cord levels of EOPs. Towards these ends, both biological and chemical approaches will be employed. The biological approaches will include rat stereotaxic surgery and intra- cerebroventricular/intrathecal/intracerebral microinjection technique, and analgesia testing (hot plate test). The chemical approaches will include radioimmunoassay for EOPs in ventricular-cisternal/intrathecal perfusate and nervous tissues of rats !exposed to nitrous oxide, and fractionation by high performance liquid chromatography (HPLC) for EOPs from perfusate and tissue samples from rats exposed to nitrous oxide. Other parameters to be monitored include inspired anesthetic agents, body temperature, blood pressure and blood chemistry. The long term goal of this continuing research is to systematically analyze the opioid nature of the drug actions and drug effects of nitrous oxide. The findings of this research should advance our understanding and knowledge of the pharmacology of nitrous oxide, which appears to be a unique and useful therapeutic and investigative opioid agent. This work should contribute to more efficacious or judicious clinical use of nitrous oxide in medicine and dentistry.

一氧化二氮是一种气态药理学试剂，具有广泛的 医学和牙科的临床应用。 尽管使用 笑气作为临床镇痛剂的作用机制 仍然有些模糊。 我们实验室最近进行的研究 和其他地方暗示了亚麻醉浓度的相互作用 一氧化二氮与内源性阿片系统的结合 基于各种 实验结果，我们假设一氧化二氮镇痛可能 结果从药物刺激的神经元释放特定的内源性 阿片肽（EOPs），随后激活中枢神经系统 阿片受体介导的阿片受体。 在过去的几年里， 我们实验室的研究工作致力于进一步阐明， 在一氧化二氮镇痛作用中阿片类物质的这种联系。 的 本研究的目的是：（1）确定亚型（S） 以及介导一氧化二氮的中枢阿片受体的位置 镇痛;（2）量化和识别人工耳蜗中增加的EOP 从麻醉的和未麻醉的两个组织中收集脑脊液灌注液， 暴露于一氧化二氮的清醒、中枢灌注大鼠;和（3） 笑气镇痛的程度与区域性 脑和脊髓水平的EOP。 为了实现这一目标，双方 将采用生物和化学方法。 生物 方法将包括大鼠立体定位手术和内- 脑室/鞘内/脑内显微注射技术， 和镇痛试验（热板试验）。 化学方法将 包括心室-脑池/鞘内EOP放射免疫测定 大鼠的灌流液和神经组织！暴露在一氧化二氮中， 通过高效液相色谱法（HPLC）分离EOP 从暴露于一氧化二氮的大鼠的灌流液和组织样本中提取的。 要监测的其他参数包括吸入的麻醉剂、身体 体温、血压和血液化学。 的长期目标 这项持续的研究是系统地分析阿片类药物的性质， 一氧化二氮的药物作用和药效 的调查结果 这项研究应该增进我们对 一氧化二氮的药理学，这似乎是一个独特的和有用的 治疗和研究阿片类药物。 这项工作应有助于 更有效或明智的临床使用一氧化二氮， 医学和牙科。