Hypersensitivity of bronchopulmonary C-fibers induced by airway mucosal inflammation: Cellular mechanisms

Stimulation of vagal bronchopulmonary C-fibers induces bronchoconstriction and hypersecretion of mucus, and is either directly or indirectly involved in eliciting cough reflex. Our recent studies have shown that the excitability of these afferents is markedly elevated in experimental conditions involving acute injury or inflammation of airway mucosa (e.g. after exposure to ozone), and cyclo-oxygenase metabolites of arachidonic acid locally released in the airways may contribute partially to the C-fiber hypersensitivity. Among the various prostanoids, prostaglandin E₂ administered by slow infusion augmented the responses of pulmonary C-fibers to both lung inflation and various chemical stimulants in anesthetized rats. The PGE₂-induced hypersensitivity of these sensory nerves could also be demonstrated in cultured neurons using the whole-cell perforated patch-clamp recording technique; PGE₂ perfusion markedly and reversibly increased both the magnitude of inward current (in voltage-clamp mode) and the number of action potentials (in current-clamp mode) evoked by capsaicin in the small-diameter nodose and jugular ganglion neurons isolated from adult rats. Moreover, PGE₂ enhanced the membrane excitability of these neurons in their response to injected current pulses and voltage steps. In conclusion, the sensitizing effect is caused by a direct action of PGE₂ on pulmonary C-fibers, and the cAMP/protein kinase A transduction cascade is probably involved.