ANESTHETIC ACTION ON OPIATE PEPTIDE GENE EXPRESSION

描述：(改编自申请者的摘要)总体目标 这个项目的关键是理解先发制人的机制 止痛--预防疼痛形成的重要过程 路径/周期。 这个问题对于治疗全身疼痛状态是至关重要的，因为疼痛状态影响 每年数以百万计的人。调查人员计划将 麻醉剂介导的抗伤害作用的生化和分子基础。 已知一些麻醉剂可提供超前止痛。 (一氧化二氮、吗啡、戊巴比妥)和其他(氟烷) 和异氟醚)。因此，具体目标包括比较这些 与以下有关的药物：1)抑制初级传入 神经传递；2)抑制神经递质的活性和/或表达 痛诱导神经可塑性的细胞内介质/标记物，如 一氧化氮和Fos；3)作为潜在的阿片效应的刺激 麻醉介导性超前镇痛的机制。此外，在 体内注射反义寡核苷酸将用于 抑制假定重要的特定细胞蛋白的合成 用于止痛，以便直接阐明潜在的分子位置 麻醉剂介导的抗伤害作用。其目标是增强当前的 对超前止痛机制的理解 阐明了治疗疼痛的可能的临床方法。

DESCRIPTION: (Adapted from the applicant's abstract) The overall goal of this project is to understand the mechanisms underlying preemptive analgesia, an important process in preventing the establishment of pain pathways/cycles. This problem is critical for treating general pain states which affect millions of people each year. The investigator plans to characterize the biochemical and molecular basis of anesthetic mediated antinociception. Some anesthetic agents are known to provide preemptive analgesia (nitrous oxide, morphine, pentobarbital) and others do not (halothane and isoflurane). Specific aims therefore include comparison of these agents with regard to: 1) inhibition of primary afferent neurotransmission; 2) inhibition of the activity and/or expression of intracellular mediators/markers of pain induced neuroplasticity such as nitric oxide and Fos; and 3) stimulation of opioid effects as potential mechanisms of anesthetic mediated preemptive analgesia. In addition, in vivo administration of antisense oligonucleotides will be used to inhibit synthesis of specific cellular proteins of putative importance for pain in order to elucidate directly potential molecular sites of anesthetic mediated antinociception. The goal is to enhance current understanding of the mechanisms involved in preemptive analgesia and to shed light on possible clinical approaches to the treatment of pain.