Peripheral cough-related sensory mechanisms

Peripheral cough-related sensory mechanisms encompass the physiological pathways involving primary afferent nerves, specifically the vagus nerve, that innervate the airways and trigger the cough reflex (Mazzone & McGovern, 2016, Frontiers in Physiology). These mechanisms rely on the activation of specialized molecular sensors, including P2X3 purinergic receptors and Transient Receptor Potential (TRP) channels like TRPV1 and TRPA1, which detect chemical, mechanical, and thermal stimuli (Chung et al., 2022, Lancet Resp Med). In pathological conditions such as chronic cough or cough hypersensitivity syndrome, these peripheral pathways become sensitized, resulting in an exaggerated response to low-level triggers, a phenomenon known as hypertussia or allotussia (Morice et al., 2020, ERJ). Pharmacological agents like Gefapixant and other P2X3 antagonists target these peripheral mechanisms to reduce the frequency of refractory or unexplained chronic cough by inhibiting the transmission of tussive signals (Smith et al., 2020, The Lancet). Understanding these peripheral sensory mechanisms is essential for the development of targeted antitussive therapies that modulate airway nerve excitability without affecting central nervous system function.

Other names

Peripheral cough reflexAirway sensory nerve mechanismsCough hypersensitivityPeripheral tussive pathwaysVagal afferent cough mechanisms

Inhibition of peripheral sensory nerve activation or sensitization by blocking specific ion channels (e.g., P2X3, TRPV1, TRPA1) or voltage-gated sodium channels to reduce the transmission of tussive signals to the central nervous system (Mazzone & McGovern, 2016, Frontiers in Physiology; Smith et al., 2020, The Lancet).