IMPORTANCE OF PERIPHERAL SITES OF ANALGESIC ACTION

外周镇痛部位的重要性

• 批准号: 2747973
• 负责人: JERRY COLLINS
• 金额: $ 18.38万
• 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/2747973
• 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（根据申请人的摘要改编）： 这项工作的目的是对能力进行系统研究 通过对中心作用的镇痛药来产生镇痛 周围神经系统。该研究旨在提供答案 到三个问题：（1）其中哪些外围受体系统 该调节疼痛的中心能够产生周围 镇痛？ （2）是系统产生的周围镇痛 在外围的或多或少地被确定为有效的 脊髓中那些相同系统产生的镇痛？ （3）是 那些人之间存在累加或协同的外围相互作用 系统以及它们之间以及低剂量的局部麻醉药？研究 将在研究人员开发的行为模型中进行 这允许在正常状态和痛觉状态下进行测试。一个 在一般下，在大鼠中产生了一只后脚的热损伤 测试了两个小时的热刺激的麻醉和戒断潜伏期 之后。如果Hypergerseia被视为差异> 1.5秒 受伤和未受伤的爪子之间的戒断潜伏期存在， 动物用于二十四小时后的镇痛测试。 此时再次记录了Hypergesia。注射药物 爪是在氟烷麻醉下进行的，然后是 停产，每15分钟测量一次提款的潜伏期 动物觉醒之后。经过处理和未经处理的爪子的潜伏期是 与检测系统性与局部镇痛作用相比。代理商 接受测试包括胆碱能，阿片类和腺苷A1的激动剂 受体，以及兴奋性氨基酸，NK1和腺苷的拮抗剂 A2受体。将尝试获取和测试新化合物 不会越过血脑屏障。