ANESTHETIC ACTION ON OPIATE PEPTIDE GENE EXPRESSION

强效镇痛药和全身麻醉药可作用于原发性疼痛调节 脊髓中的回路来改变伤害性信息的流动。 这些药物可以改变初级传入输入，改变下行活动， 直接影响调节中间神经元的放电。 但是，在阻止 在给药期间的疼痛感知，这些 外源性物质也可改变内源性脑活动 这些系统通常会被招募来调节伤害性输入。 最近的证据强烈表明，麻醉剂和镇痛剂诱导的 神经元功能的改变可对神经元的活动产生显著影响， S 主要节段性和内源性CNS疼痛调节系统， 使用阿片肽作为神经递质。 因此，我们将重点关注 表达前脑啡肽原和前强啡肽原基因的神经元， 它们利用这些基因的翻译产物来调节疼痛， 传递者之间的相互关系进行调查， 内源性镇痛 特异性神经递质功能活动的特异性监测 神经元群体难以实现。 然而，原位定量 杂交技术允许评估神经元的程度， 前脑啡肽原和前强啡肽原基因在正常脑组织中的表达 e 细胞群 这些方法可以检测到实质性和快速的变化 这些基因在疼痛反应神经元中的细胞表达， 增强或减少初级传入输入。 本文提出的研究将监测这些基因的神经元表达， S 在麻醉/镇痛方案期间，被认为通过以下方式起作用：（a） 阻断传入冲动的传导，（B）刺激 下降的内源性镇痛系统，（c）模仿活动， 节段性阿片肽镇痛系统，和（d）阻断意识 对疼痛的感知 这些研究将评估药物引起的 阿片肽基因的功能相关表达低于基线， 刺激条件作为这些临床使用的影响的一个指标 外源性镇痛药对内源性镇痛系统功能的影响。 这项工作应提高了解这些治疗剂如何影响 不 内源性镇痛的能力可能会产生显著的 y 改善疼痛管理的临床策略。

Potent analgesics and general anesthetics can act on primary pain-modulatin circuits in the spinal cord to alter the flow of nociceptive information. These drugs can change primary afferent input, alter descending activity, o directly impact the firing of modulating interneurons. However, in blockin the perception of pain during the period when they are administered, these exogenous agents could also change the activities of the endogenous brain systems that would normally be recruited to modulate nociceptive inputs. Recent evidence strongly suggests that anesthetic- and analgesic-induced changes in neuronal function could exert significant impact on the activiti s of the principal segmental and endogenous CNS pain-modulating systems that use opioid peptides as neurotransmitters. Therefore, we will focus on neurons which express the preproenkephalin and preprodynorphin genes and which use the translation products of these genes as pain-modulating transmitters to investigate the inter-relationship between exogenous and endogenous analgesia. Neurotransmitter-specific monitoring of the functional activity of specific neuronal populations is difficult to achieve. However, quantitated in situ hybridization techniques allow assessment of the extent of neuronal expressional of preproenkephalin and preprodynorphin genes in the appropria e cell populations. These approaches can detect substantial and rapid change in the cellular expression of these genes in pain-responsive neurons with enhancement or reductions in primary afferent inputs. The studies proposed here will monitor the neuronal expression of these gen s during anesthetic/analgesic regimens that are thought to act by: (a) blocking conduction of afferent impulses, (b) simulating activity in descending endogenous analgesic systems, (c) mimicking activity in the segmental opiate peptide analgesic systems, and (d) blocking conscious perception of pain. The studies will evaluate drug-induced changes in the function-related expression of the opioid peptide genes under baseline and stimulated conditions as one index of the impact of these clinically-used exogenous analgesic agents on the function of endogenous analgesic systems. This work should improve understanding of how these therapeutic agents affe t the capacity for endogenous analgesia in a way that might yield significant y improved clinical strategies for pain management.