Respiratory tract sensory C-fiber (C-fiber) (C-fiber)

Respiratory tract sensory C-fibers are unmyelinated, slow-conducting vagal afferent nerves that serve as primary sensors for noxious stimuli in the airways [1]. These fibers are characterized by their sensitivity to capsaicin, which activates the Transient Receptor Potential Vanilloid 1 (TRPV1) channels expressed on their terminals [2]. When stimulated by chemical irritants, inflammatory mediators (e.g., bradykinin, prostaglandins), or mechanical stress, these nerves trigger protective reflexes such as cough and bronchoconstriction [3]. Furthermore, they release sensory neuropeptides like Substance P and Calcitonin Gene-Related Peptide (CGRP), which mediate neurogenic inflammation, including vasodilation and edema [4]. In pathological conditions like chronic refractory cough or asthma, these fibers often exhibit hypersensitivity, leading to exaggerated responses to innocuous stimuli [5]. Pharmacological targeting of these nerves involves either desensitizing the fibers using capsaicinoids or inhibiting specific ion channels like TRPV1, TRPA1, and P2X3 to reduce neuronal excitability and alleviate symptoms [6]. Clinical trials for chronic cough have successfully targeted the P2X3 receptor on these fibers, demonstrating significant reductions in cough frequency [5]. However, modulating these nerves carries risks such as the suppression of the protective cough reflex and potential side effects like taste disturbance or thermal dysregulation depending on the specific receptor targeted [6].

Other names

Capsaicin-sensitive vagal afferent nerveBronchopulmonary C-fiberPulmonary C-fiberNociceptive airway afferentVagal C-fiberRespiratory tract sensory C-fibers / peripheral capsaicin-sensitive vagal afferent nerves

Antagonism of P2X3, TRPV1, or TRPA1 receptors to inhibit neuronal firing; Desensitization of nerve terminals via TRPV1 agonists.