Neurophysiology of Pain Adaptation and Hyperalgesia

疼痛适应和痛觉过敏的神经生理学

基本信息

批准号：
7215150
负责人：
ROBERT H LA MOTTE
金额：
$ 36.82万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1978
资助国家：
美国
起止时间：
1978-07-01 至 2008-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7215150
关键词：
Action Potentials Address Affect Animal Model Antibodies Axon Behavior Bradykinin Brain-Derived Neurotrophic Factor CALCA gene Calcitonin Gene-Related Peptide Cations Cells Chronic Code Cutaneous Dyes Excision Exhibits Fiber Fluorescent Dyes Ganglia Human Hyperalgesia In Vitro Incidence Inflammation Inflammatory Iontophoresis Label Link Measures Mediator of activation protein Membrane Modeling Muscle Myxoid cyst Neuroglia Neuronal Injury Neurons Neuropeptides Nociception Paresthesia Perfusion Peripheral Posterior Horn Cells Potassium Preparation Principal Investigator Property Prostaglandins Rattus S100A12 gene Sensory Serotonin Sodium Spinal Ganglia Stimulus Substance P Temperature Testing capsaicin receptor chemical property human S100A12 protein in vivo inflammatory neuropathic pain insight neurobiotin neurochemistry neuronal cell body neuronal excitability neurophysiology novel pain adaptation painful neuropathy patch clamp programs receptive field receptor receptor expression research study response size spinal nerve posterior root transmission process voltage voltage/patch clamp

项目摘要

DESCRIPTION (provided by applicant): In an animal model of human neuropathic pain, a chronic compression of the dorsal root ganglion (CCD) in rat induces some cell bodies (somata) in the ganglion to become hyperexcitable, spontaneously active and responsive to inflammatory mediators (IMs), such as serotonin, bradykinin or prostaglandin. Little is known of the sensory, neurochemical and electrophysiological properties of these intact, hyperexcitable neurons. The questions addressed in this proposal focus on the hyperexcitability of CCD somata: What are their receptive-field properties and neurochemical content? How do action potentials, originating in the dorsal root ganglion (DRG) and modulated by IMs, affect the coding and transmission of peripheral sensory information? What changes in voltage-gated ionic currents contribute to the somal hyperexcitability and responses to IMs? We have developed a novel preparation that superfuses the dorsal root ganglion (DRG) in vivo, allowing us to record from functionally identified neurons and chemically modulate the excitability of their somata while stimulating their receptive fields. In other experiments, we will combine current- and voltage-clamp patch recording from dissociated somata to examine the contribution of hyperpolarization-activated cation current, and voltage-gated potassium and sodium currents to CCD-induced changes in excitability and responses to IMs. The results will provide novel insights into the cellular mechanisms of the enhanced neuronal excitability contributing to neuropathic and inflammatory pain and hyperalgesia.

描述（由申请人提供）：在人类神经性疼痛的动物模型中，大鼠背侧根神经节（CCD）的慢性压缩可在神经节中诱导某些细胞体（SOMATA），使其过度兴奋，自发地活跃，对炎症介质（IMS），例如Serotanin，Bradynin，bradynin，Bradyplandin，prostaglinain，prostandinin，抗炎。这些完整的，过度可见的神经元的感觉，神经化学和电生理特性知之甚少。本提案中解决的问题侧重于CCD SOMATA的过度兴奋性：他们的接受场特性和神经化学含量是什么？源自背根神经节（DRG）并受到IMS调制的动作电位如何影响外围感觉信息的编码和传输？电压门控离子电流的哪些变化有助于对IMS的过度刺激性和对IMS的反应？我们已经开发了一种新型的制剂，该制剂在体内超级构成背根神经节（DRG），使我们能够从功能鉴定的神经元中记录并化学调节其somata的兴奋性，同时刺激其接受场。在其他实验中，我们将结合分离的somata的电流和电压钳贴片，以检查超极化激活的阳离子电流的贡献，以及电压门控钾和钠电流对CCD诱导的兴奋性变化和对IMS的反应的变化。结果将提供有关增强神经元兴奋性的细胞机制的新见解，这些兴奋性有助于神经性和炎症性疼痛和痛觉过敏。