Effect of codeine on the inspiratory and expiratory burst pattern during fictive cough in cats

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.