Cough sensory mechanism -- Multiple sensor theory in airway mechanosensory units

Abstract

Two doctrines: one-sensor theory (OST) and line-labeled theory (LLT) significantly influences our data interpretation in lung sensory field. In OST, one afferent axon connects to a single sensor. In LLT, different sensors send signals to different brain regions to evoke reflex. Thus, lung inflation activates slowly adapting receptors (SARs) and send signals to inhibit breathing (inhibitory line), causing Hering-Breuer reflex. The inflation and deflation stimulate rapidly adapting receptors (RARs) to send signals to stimulate breathing (excitatory line), producing the Hering-Breuer deflation reflex. Our physiological and morphological studies demonstrate numerous sensors up to 4 different types may be housed within a unit, i.e., an axon connects to many heterogeneous sensors (multiple-sensor theory, MST). In addition to SARs and RARs, there are deflation-activated slowly adapting (dSARs) or rapidly adapting receptors (dRARs). They work together to determine the unit behavior. For example, SAR or RAR units may respond to deflation if they house dSARs responsible for the Hering-Breuer deflation reflex. MST requires a conceptual shift because different types of information carried in an afferent axon violates conventional doctrines. Data generated over last eight decades under OST require re-interpretation. For example, based on LLT scientists believe “SARs do not cause cough”: their activation on deep lung inflation does not evoke cough. Similarly, deep inspiration and expiration activate RARs, but not cough. Therefore, SARs and RARs are excluded from the cough initiation mechanism. MST posits discharge pattern and timing dictates reflex response. It follows that, in the mechanosensory afferent pathway, continuous discharge (during sustained inflation) produces apnea and cyclic discharge facilitates respiratory rate. Therefore, there is no reason to exclude punctate-associated irregular surging discharge from cough initiation. Indeed, mechanosensors have highest density in large airways, punctate stimulation activates all four types of sensors and their coactivation significantly enhances afferent input. These thick myelinated afferents have the highest conduction velocity and discharge frequency and connect to inspiratory and expiratory neurons monosynaptically to perform effective cough action. Decades of research data support activation of this system can evoke powerful inspiratory and expiratory muscle responses. Blocking it eliminates cough response. While punctate stimulation also activates C fiber and high threshold Ad fiber sensors and may produce cough, the mechanosensory units are most important for punctate-induced cough. (Supported by a VA Merit Review Award (PULM-024-17S) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.