NOCICEPTORS AND GLUTAMATE RECEPTORS

描述(摘自申请者的摘要)：皮肤伤害性感受器是一种 一组不同种类的外周感觉神经元，感觉到有害物质， 在外周产生损伤刺激并将该信号传输到中枢 神经系统。他们从外围和中央扩展其流程 胞体位于背根神经节(DRG)。的主要站点 这些无髓和轻度中央投射的终止 有髓纤维主要分布在脊髓板浅层(I和II)。 脊髓背角。有多个伤害感受器亚群， 背根神经节(DRG)内的胞体。它们可以根据感官进行分组 形态，通过细胞内标记，如多肽，或通过表面标记，如 正如Dodd和Jessell(1985)所发展和刻画的那样。我们将使用 免疫细胞化学鉴定背根节伤害性感受器亚群。我们将测试 几种伤害性感受器表达的个体群体 特性包括低阈值和高阈值热量和辣椒素敏感性， 用钙离子成像和电生理学测量反应。红藻氨酸和 AMPA受体在DRG神经元亚群上表达，包括 功能识别的伤害感受器，尽管伤害感受器的亚群 目前还没有确定。海人藻酸和AMPA受体的表达 伤害性感受器被认为有助于检测破坏性刺激 《在皮肤里》(Carlton和CoggesHall，1995；Jackson和Hargreaves，1995)。那里 外周血红藻酸和AMPA受体的免疫细胞化学证据 表达(CoggesHall和Carlton，1998) 转导机制。有生理学证据表明背根神经节突起 神经节本身的中枢对Kainate作出反应，建议使用Kainate或AMPA 受体也可能在伤害性感受器的中央终端起作用。 (Agrawal和Evans，1986)。使用脊髓切片准备与 已鉴定的伤害性感受器和背角的附着背根及其共培养 神经元，我们将研究AMPA和海人藻酸受体在哪里表达 对DRG至关重要，特别是它们是否在 伤害性感觉神经末梢。我们将确定受体激活的影响 从初级传入终末释放谷氨酸。

DESCRIPTION (adapted from applicant's abstract): Cutaneous nociceptors are a heterogeneous group of peripheral sensory neurons that sense noxious, damage-causing stimuli in the periphery and transmit that signal to the central nervous system. They extend their processes peripherally and centrally from cell bodies located in the dorsal root ganglia (DRG). The primary site of termination of the central projection of these unmyelinated and lightly myelinated fibers is predominantly in the superficial laminae (I and II) of the spinal cord dorsal horn. There are multiple subpopulations of nociceptors with cells bodies in the dorsal root ganglion (DRG). They can be grouped by sensory modality, by intracellular markers such as peptides, or by surface markers such as those developed and characterized by Dodd and Jessell (1985). We will use immunocytochemistry to identify DRG nociceptor subpopulations. We will test individual populations of nociceptors for expression of several nociceptive properties including low and high threshold heat and capsaicin sensitivity, using Ca2+ imaging and electrophysiology to measure responses. Kainate and AMPA receptors are expressed on subpopulations of DRG neurons, including functionally identified nociceptors, although the subpopulations of nociceptors have not yet been identified. Kainate and AMPA receptors expressed by nociceptors have been suggested to contribute to detection of damaging stimuli in the skin (Carlton and Coggeshall, 1995; Jackson and Hargreaves, 1995). There is immunocytochemical evidence for peripheral kainate and AMPA receptor expression (Coggeshall and Carlton, 1998) that could underlie such a transduction mechanism. There is physiological evidence that DRG neurites central to the ganglion itself respond to kainate, suggesting kainate or AMPA receptors may have a function at the central terminals of nociceptors, as well (Agrawal and Evans, 1986). Using the spinal cord slice preparation with attached dorsal root and co-cultures of identified nociceptors and dorsal horn neurons, we will investigate where AMPA and kainate receptors are expressed central to the DRG and specifically whether they are expressed on the nociceptor nerve terminals. We will determine the impact of receptor activation on glutamate release from the primary afferent terminals.