Regulation of the Cough Reflex

咳嗽反射的调节

• 批准号: 6736973
• 负责人: DONALD C BOLSER
• 金额: $ 31.52万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6736973
• 关键词: brain stem; bronchomotion; cats; codeine; electromyography; expectorant /mucolytic; larynx; muscle relaxants; neuropathology; neurophysiology; pulmonary respiration; respiration regulatory center; respiratory disorder chemotherapy; respiratory muscles; respiratory pharmacology; respiratory reflex; trachea

DESCRIPTION (provided by applicant): Cough is the most common reason why sick patients visit physicians in the US. The long-range goal of this research is to delineate the neurogenic mechanisms by which cough is produced and regulated. The central hypothesis of this research is that the cough motor pattern is produced by an assembly of components that includes a novel regulatory element responsible for controlling the behavior of a reconfigured respiratory pattern generator. Moreover, the novel regulatory components that control laryngeal and tracheobronchial cough are not identical. The rationale for the proposed research is that once the functional organization of the brainstem cough pattern generation system is established, the mechanisms responsible for the production of pathological cough can be identified. The specific aims of the project are: 1) Determine the role of modulation of the expiratory phase in the regulation of the tracheobronchial and laryngeal cough motor patterns, 2) Determine the functional organization of the central regulatory system for tracheobronchial and laryngeal cough, 3) Determine the role of brainstem expiratory motor pathways in the antitussive-sensitive regulatory system for tracheobronchial cough, 4) Determine the role of spinal expiratory motor pathways in the antitussive-sensitive regulatory system for cough. In the first aim, key regulatory mechanisms controlling the frequency and magnitude of repetitive tracheobronchial and laryngeal cough will be determined by altering of the excitability of each. Our preliminary data suggest a) that the frequency of repetitive coughing is primarily controlled by modulation of the duration of the latter part of the cough expiratory phase, and b) that separate regulatory mechanisms are responsible for the control of the frequency and intensity of repetitive coughing. In support of the second aim, preliminary findings suggest differential sensitivity of tracheobronchial and laryngeal cough to antitussive drugs and thus divergent central regulatory mechanisms for each. In the third aim, we test a model that predicts the presence of a tracheobronchial cough gating mechanism that is presynaptic to medullary and spinal expiratory motor pathways. This gating mechanism is sensitive to antitussive drugs. The sensitivity of rostral and caudal medullary expiratory neurons to antitussive drugs will be determined during breathing and cough to differentiate between inhibition or disfacilitation of these neurons by these compounds. In the fourth aim, antitussive drugs will be delivered intrathecally while monitoring expiratory motor drive during cough to determine the role of spinal pathways in the suppression of expiratory motor discharge. The results of these experiments will provide an important test of the proposed functional organization of the cough pattern generator. Furthermore, this project will test the proposed roles of medullary and spinal cellular elements that contribute to the generation and control of expiratory motor discharge during cough.

描述（由申请人提供）：咳嗽是美国患者就诊的最常见原因。这项研究的长期目标是阐明咳嗽产生和调节的神经机制。本研究的中心假设是，咳嗽运动模式是由组件的组装产生的，该组件包括负责控制重新配置的呼吸模式发生器的行为的新型调节元件。此外，控制喉和气管支气管咳嗽的新的调节成分是不相同的。这项研究的基本原理是，一旦脑干咳嗽模式生成系统的功能组织建立起来，就可以确定病理性咳嗽产生的机制。该项目的具体目标是：1）确定呼气相的调节在气管支气管和喉咳嗽运动模式的调节中的作用，2）确定气管支气管和喉咳嗽的中枢调节系统的功能组织，3）确定脑干呼气运动通路在气管支气管咳嗽的止咳敏感调节系统中的作用，4）确定脊髓呼气运动通路在止咳敏感性咳嗽调节系统中的作用。在第一个目标中，控制重复性气管支气管和喉咳嗽的频率和幅度的关键调节机制将通过改变每个的兴奋性来确定。我们的初步数据表明：a）重复性咳嗽的频率主要是通过调节咳嗽呼气相后半部分的持续时间来控制的，和B）单独的调节机制负责控制重复性咳嗽的频率和强度。支持第二个目标，初步研究结果表明，气管支气管和喉咳嗽的止咳药物的不同敏感性，从而分歧的中央调节机制。在第三个目标中，我们测试了一个模型，预测存在的气管支气管咳嗽门控机制，是突触前髓和脊髓呼气运动通路。这种门控机制对镇咳药敏感。将在呼吸和咳嗽期间测定延髓头端和尾端呼气神经元对止咳药物的敏感性，以区分这些化合物对这些神经元的抑制或障碍。在第四个目标中，将鞘内递送止咳药物，同时监测咳嗽期间的呼气运动驱动，以确定脊髓通路在抑制呼气运动放电中的作用。这些实验的结果将提供咳嗽模式生成器的所提出的功能组织的重要测试。此外，这个项目将测试提出的作用，髓和脊髓细胞成分，有助于产生和控制呼气运动放电在咳嗽。