Sulfur-dioxide exposure increases TRPV1-mediated responses in nodose ganglia cells and augments cough in guinea pigs

The objective of the present experiments was to study the effects of pulmonary inflammation induced by subacute Sulfur-dioxide (SO2) exposure on capsaicin-induced responses in isolated primary vagal sensory neurons and cough. Additionally, we examined the effects of SO2 exposure on respiratory function and lung histology. All experiments were conducted 24 h after 4 days of subacute SO2 (1000 ppm, 3 h/day for 4 days) exposure. In in vitro experiments, intracellular Ca2+ concentrations were measured in single nodose ganglia cells isolated from SO2 treated and control guinea pigs, using a fluorescence-based methodology. In nodose ganglia cells from SO2-exposed animals, intracellular Ca2+ responses evoked by capsaicin (1×10−7 and 1×10−6 M) were significantly augmented (87% and 59%, respectively) compared to nodose ganglia from control animals. In vivo experiments, cough responses induced by a submaximal dose of aerosolized capsaicin (30 μM) were increased approximately 50% in SO2 exposed animals compared to control animals. The enhanced cough response produced by SO2 was inhibited by the corticosteroid, dexamethasone (10 mg/kg, p.o. b.i.d for 4 days and 10 mg/kg, p.o. once on day 5). In separate experiments, guinea pigs exposed to SO2 displayed a decrease in respiratory frequency and minute ventilation and an increase in enhanced pause (PenH), a surrogate measure for pulmonary obstruction. Associated with the SO2-induced increase in cough and changes in respiratory parameters was an increase in BAL neutrophils. BAL neutrophil counts were 5±4 and 691±141 cells×103/ml for air and SO2-exposed animals, respectively. The neutrophillic inflammation induced by SO2 was attenuated by dexamethasone treatment. Finally, staining for collagen, smooth muscle and goblet cells showed inflammation, remodeling and goblet cell metaphasia in the SO2-exposed animals. Our results demonstrate that SO2 exposure enhances TRPV1 receptor function at the level of the nodose ganglia. This effect occurs in parallel with an increase sensitivity of the cough response to capsaicin.