Satellite Glial and Sensory Coding: Implications for Pain

卫星胶质细胞和感觉编码：对疼痛的影响

• 批准号: 7167420
• 负责人: ROBERT H LA MOTTE
• 金额: $ 17.86万
• 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 2008-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7167420
• 关键词: Afferent Neurons; Area; Astrocytes; Behavior; Behavioral; Buffers; Calcium; Calcium Signaling; Cell membrane; Chemicals; Chronic; Code; Communication; Data; Electrophysiology (science); Endothelin-1; Exhibits; Exploratory/Developmental Grant; Future; Ganglia; Hyperalgesia; Image; In Vitro; Inflammation; Injury; Laboratories; Link; Methods; Modeling; Myxoid cyst; Neurobiology; Neuroglia; Neurons; Neuropathy; Nociception; Pain; Peripheral; Physiological; Play; Potassium; Preparation; Property; Rattus; Role; Sensory; Signal Transduction; Spinal Ganglia; Stimulus; Surface; Testing; Topical application; Trauma; allodynia; cell type; in vivo; neurochemistry; neuronal cell body; novel; painful neuropathy; patch clamp; receptive field; response

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（由申请人提供）：初级感觉神经元的细胞体（体细胞）和初始轴突段被由独立的卫星胶质细胞组成的鞘所包裹，每个细胞都有自己的质膜。我们对背根神经节中的神经胶质的生理特性以及它们发送和接收的信号知之甚少。与星形胶质细胞类似，卫星胶质细胞可能与它们所包裹的神经元和非神经元细胞进行双向离子和化学通讯。一个主要的问题是卫星神经胶质是否根据其神经元是否具有伤害性或非伤害性而具有不同的功能特性。另一个问题是，卫星神经胶质的异常特性是否在神经节创伤或炎症后引起神经元的高兴奋性和异位放电，从而在神经痛中发挥作用。在此基础上，我们探索了电生理学和成像技术在大鼠感觉神经元卫星胶质生理特性研究中的新应用。我们将对可视化神经元体的卫星胶质细胞进行膜片钳电生理记录（体外）和钙信号成像（体内）。利用来自神经元体的细胞内记录，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信。此外，我们将探索在背根神经节（神经性疼痛的CCD模型）的慢性压迫后，这些神经胶质特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细胞体的兴奋性，并产生异常性痛觉和痛觉过敏。R21旨在对卫星胶质细胞的生理特性及其与感觉神经元在正常和神经性疼痛机制中的关系提供初步数据和新的假设。