Experimental models and mechanisms of enhanced coughing

Abstract

Enhanced coughing can be produced in a variety of animal models, including the guinea pig, cat, dog and pig. Typically, airway inflammation has been produced by sensitization, exposure to cigarette smoke, sulphur dioxide or angiotensin-converting enzyme inhibitors. In some of these models, inflammatory mediators such as bradykinin and tachykinins have been shown to contribute to the enhanced coughing. While most of these studies have focussed on peripheral mechanisms, increases in central excitability of the cough reflex have been shown to occur as a result of airway inflammation. As such, we propose that enhanced coughing in pathological conditions is the result of plastic changes in both peripheral and central neural elements. Furthermore, we present a modified model of the neurogenesis of cough that takes into account peripheral and central plasticity induced by mediators of inflammation.

Fig. 1

Model of the peripheral and central elements of the neurogenic mechanism for cough, highlighting the proposed effects of inflammation. The model is modified from Bolser and Davenport[29] and depicts: (a) augmented tracheal cough receptor[30] activity, (b) laryngeal cough receptors, (c) tracheal and laryngeal relay neurones (interneurones), (d) convergent relay neurones in the NTS and medial reticular formation that receive synaptic input from both tracheal and laryngeal interneurons, (e) a tracheobronchial gating mechanism, (f) a laryngeal gating mechanism that is functionally subdivided into elements controlling excitability of the cough/respiratory pattern generator[31] and the magnitude of expiratory motor drive, and (g) inspiratory and expiratory premotor neurons. Pulmonary slowly adapting stretch receptors facilitate laryngeal cough and have a permissive effect on tracheobronchial cough [32,33]. These elements have been omitted from the model for clarity.