Bolser D C, DeGennaro F C
Department of Allergy, Schering-Plough Research Institute, Kenilworth, NJ 07033-0539.
Brain Res. 1994 Oct 31;662(1-2):25-30. doi: 10.1016/0006-8993(94)90792-7.
Experiments were conducted to study the effect of the opioid, codeine, on different components of the cough motor pattern. Midcollicular decerebrate cats were paralyzed and artificially ventilated by a pump triggered by the phrenic neurogram. Inspiratory (phrenic) and expiratory (cranial iliohypogastric) neurograms were recorded. Fictive cough was produced by mechanical stimuli applied to the intrathoracic trachea. Codeine (0.03-1.0 mg.kg-1, i.v.) decreased cough frequency (average number of coughs per stimulus trial), expiratory burst amplitude, and inspiratory burst amplitude in a dose-dependent manner. The maximum reduction in cough frequency and expiratory amplitude produced by codeine was 80-90% for both parameters. However, codeine was more potent in reducing cough frequency (ED50 = 0.1 mg.kg-1) than expiratory burst amplitude (ED50 = 0.35 mg.kg-1). The maximum observed reduction of inspiratory burst amplitude elicited by codeine was approximately 40%. There was a positive linear relationship between phrenic and cranial iliohypogastric burst amplitudes during fictive cough (r = 0.82, P < 0.001). Codeine destabilized the motor pattern during fictive cough by disrupting this relationship between inspiratory and expiratory burst amplitudes. We conclude: (a) the central pattern generator for cough is functionally organized into a cough frequency generator, an expiratory burst amplitude generator and an inspiratory burst amplitude generator, each of which have different sensitivities to codeine (b) there exists a specific codeine-sensitive neural mechanism matching the relative magnitude of central drive to inspiratory and expiratory motoneurons during cough.
开展了实验以研究阿片类药物可待因对咳嗽运动模式不同组成部分的影响。在中脑水平去大脑的猫身上进行实验，使其瘫痪，并通过由膈神经电图触发的泵进行人工通气。记录吸气（膈神经）和呼气（髂腹下神经）神经电图。通过对胸内气管施加机械刺激来诱发模拟咳嗽。静脉注射可待因（0.03 - 1.0 mg·kg⁻¹）以剂量依赖性方式降低咳嗽频率（每次刺激试验的平均咳嗽次数）、呼气爆发幅度和吸气爆发幅度。可待因对咳嗽频率和呼气幅度的最大降低幅度在两个参数上均为80 - 90%。然而，可待因在降低咳嗽频率（ED50 = 0.1 mg·kg⁻¹）方面比降低呼气爆发幅度（ED50 = 0.35 mg·kg⁻¹）更有效。可待因引起的吸气爆发幅度的最大观察到的降低约为40%。在模拟咳嗽期间，膈神经和髂腹下神经爆发幅度之间存在正线性关系（r = 0.82，P < 0.001）。可待因通过破坏吸气和呼气爆发幅度之间的这种关系，使模拟咳嗽期间的运动模式不稳定。我们得出结论：（a）咳嗽的中枢模式发生器在功能上被组织成一个咳嗽频率发生器、一个呼气爆发幅度发生器和一个吸气爆发幅度发生器，每个发生器对可待因具有不同的敏感性；（b）存在一种特定的对可待因敏感的神经机制，在咳嗽期间匹配对吸气和呼气运动神经元的中枢驱动的相对大小。
