Brainstem Structures Involved in the Generation of Reflex Cough

Cough is a very important motor act that may be voluntary, behavioral, or simply reflex. Cough shares many similarities with pain at both peripheral and central levels. It shows several components (sensory-discriminative, affective, reflex) that reach their maximum complexity in awake animals and especially in humans who display even placebo/nocebo effects. This chapter is primarily focused on reflex cough triggered by nociceptive stimulation of the tracheobronchial tree and mediated by brainstem neuronal mechanisms. Cough-related inputs are conveyed to the caudal nucleus tractus solitarii (cNTS) that in turn projects to the brainstem respiratory network that is reconfigured to generate the cough motor pattern. A high degree of modulatory influences are exerted on NTS second-order neurons and on the brainstem respiratory network by inputs arising from sensory nerves and higher brain areas. Several medullary structures have key functions in cough production, but, at present, at least two of them proved to be strategic sites of action for centrally active drugs, i.e., the cNTS and the caudal ventral respiratory group (cVRG). Drugs microinjected into these medullary structures cause downregulation or upregulation of the cough reflex. It has been shown that inhibition and disinhibition are prominent regulatory mechanisms of the reflex and that both the cNTS and the cVRG are essential for the generation of the overall cough motor pattern. Studies on the basic neural mechanisms subserving the cough reflex may provide hints for further cough researches or novel therapeutic approaches.