IMPORTANCE OF PERIPHERAL SITES OF ANALGESIC ACTION

外周镇痛部位的重要性

• 批准号: 6150331
• 负责人: JERRY COLLINS
• 金额: $ 18.05万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-02-01 至 2002-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6150331
• 关键词: adenosine; analgesics; centrally acting drug; combination chemotherapy; drug interactions; drug receptors; hyperalgesia; laboratory rat; local anesthetics; neurotransmitter receptor; opioid receptor; peripheral nervous system; pharmacokinetics; stimulus /response; stimulus interval

DESCRIPTION (adapted from applicant's abstract): The goal of this work is to conduct a systematic study of the ability of centrally acting analgesic agents to produce analgesia by actions on the peripheral nervous system. The study is designed to provide answers to three questions: (1) What peripheral receptor systems among those that modulate pain centrally are capable of producing peripheral analgesia? (2) Is the peripheral analgesia produced by the systems identified as efficacious in the periphery greater or less than the analgesia produced by those same systems within the spinal cord? (3) Are there additive or synergistic peripheral interactions between those systems and between them and low doses of local anesthetics? Studies will be carried out in a behavioral model developed by the investigator which permits testing in both a normal and a hyperalgesic state. A thermal injury to one hind foot is created in a rat under general anesthesia and withdrawal latency to a thermal stimulus tested two hours later. If hyperalgesia, considered as a difference >1.5 sec in withdrawal latency between injured and uninjured paws, is present, the animal is used for analgesia testing twenty-four hours later. Hyperalgesia is again documented at this time. Drug injection into one paw is carried out under halothane anesthesia, which is then discontinued, and latencies to withdrawal measured every 15 minutes after the animal awakens. Latencies of treated and untreated paws are compared to detect systemic versus local analgesic effects. Agents to be tested include agonists at cholinergic, opiate and adenosine A1 receptors, and antagonists at excitatory amino acid, NK1 and adenosine A2 receptors. Attempts will be made to obtain and test new compounds that do not cross the blood-brain barrier.

描述（改编自申请人摘要）： 这项工作的目标是进行系统的研究能力 中枢作用镇痛剂，通过作用于 周围神经系统这项研究旨在提供答案 三个问题：（1）哪些外周受体系统，其中 能够产生外周的 镇痛法(2)外周镇痛是由系统产生的 被确定为在外周中有效的大于或小于 脊髓内的这些相同系统产生的镇痛作用？(3)是 在这些物质之间存在着附加的或协同的外围相互作用， 系统和他们之间的低剂量的局部麻醉剂？研究 将在研究人员开发的行为模型中进行 其允许在正常和痛觉过敏状态下进行测试。一 对一只后足的热损伤在一般条件下的大鼠中产生， 对热刺激的麻醉和退缩潜伏期测试两小时 后如果痛觉过敏，则认为差异>1.5秒， 受伤和未受伤的爪子之间的撤退潜伏期，是存在的， 24小时后将动物用于镇痛试验。 此时再次记录到痛觉过敏。药物注射到一个 爪在氟烷麻醉下进行，然后 停药，每15分钟测量一次停药时间 动物醒来后处理和未处理爪的乳量是 来检测全身和局部的镇痛效果。剂以 包括胆碱能激动剂、阿片和腺苷A1 受体和兴奋性氨基酸、NK 1和腺苷的拮抗剂 A2受体。将尝试获得和测试新的化合物 不能穿过血脑屏障