ANESTHETIC ACTION ON OPIATE PEPTIDE GENE EXPRESSION

强效止痛药和全身麻醉药可作用于初级痛觉调制 脊髓中改变伤害性信息流的回路。 这些药物可以改变初级传入输入，改变下行活动，或 直接影响调制中间神经元的放电。但是，在阻止中 在给药期间对疼痛的感知，这些 外源性物质也可以改变内源性大脑的活动。 正常情况下被招募来调节伤害性输入的系统。 最近的证据有力地表明，麻醉剂和止痛剂诱导的 神经功能的改变可能会对活动产生重大影响 S 主要的节段性和内源性中枢神经系统痛觉调制系统 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以及 它们使用这些基因的翻译产物作为疼痛调节 传递体研究外源和外源基因之间的相互关系 内源性止痛。 神经递质特异性监测特异体的功能活动 神经元种群很难实现。然而，原位定量 杂交技术可以评估神经元的范围 前脑啡肽原和前强啡肽原基因在专属神经节中的表达 E 细胞群。这些方法可以检测到重大且快速的变化 在痛反应神经元中这些基因的细胞表达 增强或减少初级传入输入。 这里提出的研究将监测这些基因的神经元表达 S 在麻醉/止痛方案期间，被认为起作用的方式有：(A) 阻断传入冲动的传导，(B)模拟活动 下行内源性止痛系统，(C)模拟脑内活动 节段性阿片肽止痛系统，以及(D)阻断意识 对疼痛的感知。这些研究将评估药物诱导的 阿片肽基因在基线和基础状态下的功能相关表达 作为这些临床使用的影响的一个指标的刺激条件 外源性止痛药对内源性镇痛系统功能的影响。 这项工作应该会增进对这些治疗剂如何作用的理解 T 内源性止痛的能力可能会产生显著的 是 改进了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.