Peripheral sensory C-fibers in airways (C-fibers)

Peripheral sensory C-fibers in the airways are unmyelinated, slow-conducting vagal afferent nerves that play a critical role in airway defense and the pathophysiology of respiratory diseases (Undem and Taylor, 2019). These fibers are primarily nociceptive, responding to a wide array of chemical irritants, inflammatory mediators such as bradykinin and prostaglandins, and mechanical stimuli (Canning et al., 2006). Upon activation, they trigger protective reflexes including cough, bronchoconstriction, and mucus secretion, and can also initiate neurogenic inflammation through the local release of neuropeptides like substance P and calcitonin gene-related peptide (CGRP) (Belvisi, 2003). In chronic inflammatory conditions like asthma and COPD, these fibers often become hypersensitive, contributing to persistent cough and airway hyperresponsiveness (Lee and Pisarri, 2001). Key molecular targets on these fibers include the P2X3 purinoceptor, the transient receptor potential vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1) channels, and voltage-gated sodium channels such as Nav1.7 and Nav1.8 (Undem and Taylor, 2019). While often discussed as a therapeutic target in respiratory medicine, it should be noted that 'Peripheral sensory C-fibers' refers to a population of nerve fibers rather than a single molecular entity.

Other names

Vagal bronchopulmonary C-fibersBronchial C-fibersPulmonary C-fibersCapsaicin-sensitive airway afferentsNociceptive airway afferents

Modulation of sensory nerve excitability via antagonism of P2X3, TRPV1, or TRPA1 receptors, or blockade of voltage-gated sodium channels (Nav1.7/1.8).