Central mechanisms IV: conscious control of cough and the placebo effect

Early animal experiments on cough developed the concept that cough was an involuntary reflex controlled from areas in the brainstem and that cough could be inhibited by centrally acting medicines such as codeine. Studies on the voluntary control of cough, the urge to cough and the placebo effect of cough medicines have demonstrated that human cough is more complex than a brainstem reflex. The efficacy and mechanism of action of centrally acting cough medicines such as codeine and dextromethorphan is now in dispute, and codeine is no longer accepted as a gold-standard antitussive. This review puts forward a cough model that includes three types of cough: (1) reflex cough, caused by the presence of food or fluid in the airway--this type of cough is not under conscious control and can occur in the unconscious subject during general anaesthesia; (2) voluntary cough--under conscious control that is abolished with general anaesthesia; (3) cough in response to sensation of airway irritation--this type of cough causes an urge to cough that initiates voluntary cough and may only be present in the conscious subject. The review proposes that human cough associated with respiratory disease is under conscious control and is mainly related to a sensation of airway irritation and an urge to cough (type 3). The review discusses the summation of sensory input from the airway in a brainstem integrator that reaches a threshold to cause reflex cough. Subthreshold conditions in the cough integrator may be perceived as an urge to cough that is under voluntary control. The cough model presented in the review has implications for the development of cough medicines as it indicates that the older view of cough medicines acting in the brainstem area to inhibit the cough reflex may need to be revised to include conscious control of cough as an important mechanism of cough in man.