IMPORTANCE OF PERIPHERAL SITES OF ANALGESIC ACTION

描述(改编自申请人的摘要)： 这项工作的目标是对能力进行系统的研究 中枢作用止痛剂通过作用于 周围神经系统。这项研究旨在提供答案 回答三个问题：(1)这些人中有哪些外周受体系统 中枢调节疼痛能够产生外周疼痛 止痛？(2)外周止痛是系统产生的吗？ 在外周识别为有效的大于或小于 脊髓内的这些系统产生的止痛？(3)是 它们之间是否存在相加或协同的外围相互作用 以及它们之间和低剂量的局麻药？研究 将在调查员开发的行为模型中进行 其允许在正常和过痛状态下进行测试。一个 一般情况下，大鼠一只后足发生热损伤 对热刺激的麻醉和戒断潜伏期测试两小时 后来。如果痛觉过敏，被认为是1.5秒内的差异 受伤和未受伤的爪子之间的撤退潜伏期是存在的， 动物24小时后用于镇痛试验。 此时，痛觉过敏再次被记录在案。注射毒品合二为一 PAW是在氟烷麻醉下进行的，然后 停用，每15分钟测量一次停药延迟 在动物醒来后。已处理和未处理的爪子的潜伏期为 比较全身止痛与局部止痛效果。代理至 包括胆碱能、阿片类和腺苷A1的激动剂 兴奋性氨基酸、NK1和腺苷的受体和拮抗剂 A2受体。将尝试获得和测试新的化合物 不会越过血脑屏障的物质。

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.