High Resolution of Mapping of Pain Ciruity in the Dorsal Horn

背角疼痛循环的高分辨率测绘

• 批准号: 7316525
• 负责人: Andrew Mark Strassman
• 金额: $ 35.84万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7316525
• 关键词: Action Potentials; Address; Area; Behavior; Cells; Class; Data; Dendrites; Depth; Elements; Genes; Glutamates; Interneurons; Investigation; Islet Cell; Islets of Langerhans; Knowledge; Lasers; Location; Maps; Methods; Neuraxis; Neurons; Nociception; Pain; Pain Map; Pain Research; Pattern; Posterior Horn Cells; Radial; Range; Relative (related person); Resistance; Resolution; Sampling; Scanning; Site; Slice; Source; Spinal; Spinal Cord; Synapses; System; Techniques; Testing; Tetrodotoxin; Time; Tissues; base; cell type; concept; dorsal horn; inflammatory neuropathic pain; insight; islet; neuronal cell body; novel; relating to nervous system; research study; response; spinal nerve posterior root; transmission process; Action Potentials; Address; Area; Behavior; Cells; Class; Data; Dendrites; Depth; Elements; Genes; Glutamates; Interneurons; Investigation; Islet Cell; Islets of Langerhans; Knowledge; Lasers; Location; Maps; Methods; Neuraxis; Neurons; Nociception; Pain; Pain Map; Pain Research; Pattern; Posterior Horn Cells; Radial; Range; Relative (related person); Resistance; Resolution; Sampling; Scanning; Site; Slice; Source; Spinal; Spinal Cord; Synapses; System; Techniques; Testing; Tetrodotoxin; Time; Tissues; base; cell type; concept; dorsal horn; inflammatory neuropathic pain; insight; islet; neuronal cell body; novel; relating to nervous system; research study; response; spinal nerve posterior root; transmission process

DESCRIPTION (provided by applicant): In recent years, pain research has made revolutionary advances at levels ranging from genes to behavior. However, one basic level of organization that has proved particularly resistant to analysis is the intrinsic circuitry underlying pain transmission and modulation within the first central relay area, the spinal dorsal horn. There is much evidence that changes in intrinsic dorsal horn interneurons contribute to plasticity underlying inflammatory and neuropathic pain, but further understanding has been limited by a dearth of methods for studying this intrinsic circuitry. In recent years a novel technique was developed that has made it possible for the first time to dissect the organization of the synaptic connectivity of closely spaced neural elements. With this technique, laser scanning photostimulation (LSPS), synaptic responses are recorded in a single neuron while focal stimulation produced by laser-induced glutamate uncaging is delivered to multiple sites in the tissue surrounding the recorded neuron. The resulting map reveals the location of local excitatory and inhibitory pre-synaptic neurons that give monosynaptic input to the recorded neuron. LSPS has transformed our knowledge of circuitry in a many areas of the central nervous system, but has not yet been used in the pain system. We now propose to use this technique to study the organization of pain (nociceptive) circuitry in the dorsal horn. The proposed experiments will map the locations of dorsal horn neurons that give rise to local excitatory and inhibitory synaptic input to lamina I projection neurons and lamina II interneurons (islet, central, vertical, and radial cells). This approach is based on the hypothesis that the pattern of intrinsic connectivity in the dorsal horn is spatially organized, and that this spatial organization is a fundamental determinant of dorsal horn function. We further hypothesize that this spatial organization differs for excitatory and inhibitory inputs, and is cell-type specific. The application of this technique to the dorsal horn will advance our understanding of the new concept of a modular organization that has been proposed from recent studies of the dorsal horn, and open up an entire field of investigation into the organization and plasticity of dorsal horn circuitry.

描述（由申请人提供）：近年来，疼痛研究已在基因到行为的水平上取得了革命性的进步。但是，事实证明，一个基本的组织水平特别抵抗分析，是第一个中央继电器区域内脊柱背侧角内疼痛传播和调节的内在电路。有很多证据表明，内在的背角中间神经元的变化有助于炎症和神经性疼痛的可塑性，但由于缺乏研究这种内在电路的方法，进一步的理解受到了限制。近年来，开发了一种新颖的技术，该技术首次可以剖析紧密间隔神经元素的突触连通性的组织。通过这种技术，激光扫描光刺激（LSP），在单个神经元中记录突触反应，而激光诱导的谷氨酸未代产生的局灶性刺激则传递到记录神经元周围组织中的多个部位。最终的图揭示了局部兴奋性和抑制性突触前神经元的位置，这些神经元给记录的神经元提供了单突触的输入。 LSP在中枢神经系统的许多区域中改变了我们对电路的了解，但尚未在疼痛系统中使用。现在，我们建议使用这种技术来研究背喇叭中疼痛（伤害感受）电路的组织。提出的实验将绘制背角神经元的位置，这些神经元引起局部兴奋性和抑制性突触输入，向椎板I投射神经元和层中II中间神经元（小岛，中央，垂直和径向细胞）产生局部兴奋性和抑制性突触输入。这种方法基于以下假设：背角中的内在连通性模式是空间组织的，并且该空间组织是背角功能的基本决定因素。我们进一步假设该空间组织在兴奋性和抑制性输入方面有所不同，并且是细胞类型的特异性。该技术在背喇叭上的应用将提高我们对最近对背角的研究提出的模块化组织的新概念的理解，并为背角电路的组织和可塑性开辟了整个研究领域。