Peripheral cough reflex pathway

The peripheral cough reflex pathway is a physiological circuit responsible for detecting and responding to airway irritants to protect the lungs from aspiration and foreign material (Mazzone & Undem, 2016). It begins with the activation of sensory nerve endings, primarily vagal afferents (C-fibers and A-delta fibers), located within the respiratory tract lining (Morice et al., 2020). These nerves express various molecular sensors, including transient receptor potential (TRP) channels like TRPV1 and TRPA1, as well as P2X3 purinergic receptors, which respond to chemical, mechanical, and inflammatory stimuli (Chung, 2020). Once activated, these peripheral receptors transmit signals to the nucleus tractus solitarius in the brainstem to initiate the cough motor program (StatPearls, 2023). In conditions such as chronic cough and cough hypersensitivity syndrome, this pathway becomes sensitized, causing a persistent and debilitating cough (Smith et al., 2020). Therapeutic strategies targeting this pathway involve the use of peripheral antitussives, such as P2X3 receptor antagonists or local anesthetics, to reduce the excitability of airway sensory nerves and alleviate the cough reflex without the systemic side effects associated with central-acting opioids (Dicpinigaitis, 2011).

Other names

Cough reflex arcVagal afferent cough pathwayPeripheral cough receptorsAirway sensory nerve pathway

Inhibition of peripheral sensory nerve activation and signal transmission from the airways to the central nervous system.