EXCITATORY AMINO ACIDS: ROLE IN PAIN & OPIOID ACTIVITY

兴奋性氨基酸：在疼痛中的作用

• 批准号: 3209169
• 负责人: ALICE A LARSON
• 金额: $ 10.92万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-04-01 至 1989-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3209169
• 关键词: afferent nerve; aminoacid analog; aminoacid inhibitor; analgesics; aspartate; axon; denervation; dorsal root; electrophysiology; glutamates; high performance liquid chromatography; histochemistry /cytochemistry; monoclonal antibody; neural transmission; neuropharmacology; opiate alkaloid; pain; radionuclide double label; spinal ganglion; thalamus

Electrophysiological studies of cultured dorsal root ganglion (DRG) cells suggest that approximately 80% of DRG neurons utilize excitatory amino acids (EAA) as neurotransmitters. Recently our laboratory has raised a monoclonal antibody specific for fixative-modified glutamate. Using this antibody, immunoreactivity was observed within the spinal trigeminal nucleus (STN), spinal cord dorsal horn and dorsal root ganglia neurons, areas known to be involved in nociception. Based on these preliminary immunohistochemical data and other results from our laboratory showing apparent glutamatergic projections from the STN to the thalamus, we hypothesize that neurons in pathways involved in nociception utilize EAAs as neurotransmitters. Furthermore, their activity may be affected by substances which are known to alter nociception, such as opioids. Our long term goal is to determine whether EAAs play a role in primary afferent and/or centrally projecting fibers involved in pain transmission and whether these EAA pathways are specifically affected by opioid and non-opioid compounds. This goal is defined by the following specific objectives: 1) to characterize the distribution of glutamate- and aspartate-like immunostaining in the DRG and spinal cord, to analyze the relationship between opioid axon terminals and EAA-containing neurons, and to ascertain if spinal EAA-containing neurons project to the thalamus; 2) to compare using HPLC analysis as well as immunostaining, the concentrations of glutamate, aspartate and other EAAs in specific areas of the spinal cord before and after dorsal rhizotomy; 3) to measure the release of EAAs from spinal tissue into CSF following peripheral nerve stimulation and injection of opioid and non-opiate compounds which are known to alter either sensory-perception or EAA activity; 4) to determine the effect of a variety of recently developed EAA-analogs on nociception, as measured by methods which selectively elicit nociception using thermal, mechanical or chemical stimuli. These studies will provide important and novel data on the role of EAAs in the spinal cord and the involvement of sigma opioid agonists in antinociception, perhaps involving blockade of EAA action.

培养的背根神经节（DRG）细胞的电生理研究 建议大约80％的DRG神经元使用兴奋性氨基 酸（EAA）作为神经递质。 最近，我们的实验室提出了 针对固定剂修饰的谷氨酸的单克隆抗体。 使用此 抗体，在脊柱三叉神经中观察到免疫反应性 细胞核（STN），脊髓背角和背根神经神经元， 已知参与伤害感受的区域。 基于这些初步 免疫组织化学数据和我们实验室的其他结果显示 从STN到丘脑的明显谷氨酸能预测，我们 假设与伤害感受有关的途径中的神经元利用EAA 作为神经递质。 此外，他们的活动可能受到 已知会改变伤害感受的物质，例如阿片类药物。 我们的长期目标是确定EAA是否在初选中发挥作用 参与疼痛传播的传入和/或集中投射纤维 以及这些EAA途径是否受阿片类药物的特异性影响 非阿片类化合物。 该目标由以下特定定义 目标：1）表征谷氨酸和 在DRG和脊髓中类似天冬氨酸样的免疫染色，以分析 阿片类药物轴突终端与含EAA神经元的关系，以及 确定含有脊柱EAA的神经元是否向丘脑发射； 2） 要使用HP​​LC分析和免疫染色进行比较 特定区域的谷氨酸，天冬氨酸和其他EAA的浓度 背侧根茎前后的脊髓； 3）测量 外周神经后，将EAA从脊柱组织释放到CSF 刺激和注射阿片类药物和非伴侣化合物 已知会改变感觉感知或EAA活性； 4）确定 各种最近开发的EAA-Analogs对伤害感受的影响， 通过通过使用热吸引伤害感受的方法来衡量 机械或化学刺激。 这些研究将提供重要的和 关于EAA在脊髓中的作用的新数据和参与 抗伤害感受吸收的西格玛阿片类药物激动剂，也许涉及EAA的封锁 行动。