Peripheral airway C-fibers and sensory neuropeptide signaling

Peripheral airway C-fibers are unmyelinated, slow-conducting sensory neurons that densely innervate the respiratory tract, including the trachea and bronchi (Barnes, 2001, PMID: 11448341). These fibers act as primary sensors for noxious stimuli, such as chemical irritants, inflammatory mediators, and environmental pollutants, primarily through the activation of ion channels like TRPV1 and TRPA1 (Geppetti et al., 2008, PMID: 18515488). Upon activation, C-fibers release sensory neuropeptides, most notably Substance P (SP) and Calcitonin Gene-Related Peptide (CGRP), from their peripheral terminals (Joos et al., 2000, PMID: 11036157). This release triggers neurogenic inflammation, which involves bronchoconstriction, microvascular leakage, and mucus hypersecretion (Groneberg et al., 2004, PMID: 15527814). In chronic respiratory diseases such as asthma, COPD, and chronic cough, these fibers often become hypersensitive, contributing to persistent symptoms and airway hyperresponsiveness (Lee & Pisarri, 2001, PMID: 11518518). Therapeutic strategies targeting this system include the use of TRPV1 antagonists to prevent fiber activation or NK1 and CGRP receptor antagonists to block the effects of released neuropeptides (Mazzone & Undem, 2016, PMID: 27432238). While promising for treating chronic inflammatory airway diseases, targeting these pathways requires careful consideration of the potential loss of protective reflexes like the cough response.

Other names

Bronchopulmonary C-fibersVagal C-fibersAirway neurogenic inflammation pathwaySensory neuropeptide signaling

Inhibition of sensory nerve activation via ion channel modulation or antagonism of neuropeptide receptors (NK1, CGRP) to reduce neurogenic inflammation.