ANESTHETIC ACTION ON OPIATE PEPTIDE GENE EXPRESSION

描述：（改编自申请人的摘要）总体目标 这个项目的目的是了解先发制人的机制， 镇痛，防止疼痛形成的重要过程 路径/循环。 这一问题对于治疗一般疼痛状态至关重要， 每年有数百万人。研究者计划描述 麻醉剂介导的抗伤害感受的生物化学和分子基础。 已知一些麻醉剂可提供超前镇痛 （一氧化二氮，吗啡，戊巴比妥）和其他不（氟烷 和异氟烷）。因此，具体目标包括比较这些 药物：1）抑制初级传入 神经传递; 2）抑制以下的活性和/或表达： 疼痛诱导的神经可塑性的细胞内介质/标记物， 一氧化氮和Fos;和3）刺激阿片样物质的作用作为潜在的 麻醉药介导的超前镇痛机制。另外在 反义寡核苷酸的体内给药将用于 抑制被认为重要的特定细胞蛋白质的合成 为了直接阐明疼痛的潜在分子位点， 麻醉剂介导的抗伤害感受。目标是增强电流 了解预先镇痛的机制， 揭示了治疗疼痛的可能临床方法。

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.