Satellite Glial and Sensory Coding: Implications-Pain

卫星胶质细胞和感觉编码：影响-疼痛

• 批准号: 7016035
• 负责人: ROBERT H LA MOTTE
• 金额: $ 22.07万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-01-10 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7016035
• 关键词: afferent nerve; calcium flux; calcium indicator; cell cell interaction; electrophysiology; glia; hyperalgesia; imaging /visualization /scanning; laboratory rat; molecular /cellular imaging; nerve injury; neuroimaging; neuronal transport; neurons; pain; potassium channel; soma; spinal ganglion; voltage /patch clamp

DESCRIPTION (provided by applicant): The cell body (soma) of the primary sensory neuron and initial axonal segment are enveloped by a sheath that consists of discrete satellite glial cells each with its own plasma membrane. We know little of the physiological properties of the glia in the dorsal root ganglion and what signals they send and receive. By analogy with astrocytes, it is possible that satellite glia engage in bi-directional ionic and chemical communication with the neurons they ensheathe and with non-neuronal cells. A major question is whether satellite glia have different functional properties according to whether their neurons have nociceptive or non-nociceptive properties. Another question is whether abnormal properties of satellite glia play a role in neuropathic pain by contributing to neuronal hyperexcitability and ectopic discharges originating in the ganglion after trauma or inflammation. With this R21 we explore the novel application of electrophysiology and imaging to the study of the physiological properties of the satellite glia of functionally identified sensory neurons in the rat. We will carry out patch-clamp electrophysiological recording (in vitro), and imaging of calcium signals (in vivo), in satellite glia of visualized neuronal somata. Using intracellular recording from the neuronal soma, we will link the properties of the neuron with the properties of the attached glia and search for bi-directional communication between the two cell types. In addition, we will explore the possibility that these glial properties and possible glial-neuronal interactions are significantly altered after a chronic compression of the dorsal root ganglion (CCD model of neuropathic pain) - an injury known to enhance the excitability of neuronal cell bodies and to produce allodynia and hyperalgesia. The R21 is intended to generate preliminary data and new hypotheses on the physiological properties of satellite glia and their relationships with their sensory neurons in the context of normal and neuropathic mechanisms of pain.

描述(申请人提供)：初级感觉神经元的细胞体(胞体)和最初的轴突段被一个鞘包裹，该鞘由离散的卫星神经胶质细胞组成，每个细胞都有自己的质膜。我们对背根神经节中胶质细胞的生理特性以及它们发送和接收的信号知之甚少。通过与星形胶质细胞的类比，星形胶质细胞可能与它们所覆盖的神经元和非神经元细胞进行双向离子和化学交流。一个主要的问题是，根据卫星胶质细胞的神经元是否具有伤害性或非伤害性，它们是否具有不同的功能属性。另一个问题是，卫星胶质细胞的异常特性是否通过促进创伤或炎症后神经节的神经元过度兴奋和异位放电而在神经病理性疼痛中发挥作用。利用这个R21，我们探索了电生理学和成像在研究大鼠功能鉴定感觉神经元卫星胶质细胞的生理特性方面的新应用。我们将在可视化神经元胞体的卫星胶质细胞中进行膜片钳电生理记录(体外)和钙信号成像(体内)。利用神经元胞体的细胞内记录，我们将把神经元的特性与附着的胶质细胞的特性联系起来，并寻找两种细胞类型之间的双向通讯。此外，我们还将探索在慢性压迫背根神经节(神经病理性疼痛的CCD模型)后，这些胶质属性和可能的神经胶质-神经元相互作用显著改变的可能性-这种损伤已知会增强神经元胞体的兴奋性，并产生超敏和痛觉过敏。R21的目的是在疼痛的正常和神经病理机制的背景下，产生关于卫星胶质细胞的生理特性以及它们与其感觉神经元的关系的初步数据和新的假设。