Real-time monitoring of nasal mucosal pH during carbon dioxide stimulation: Implications for stimulus dynamics

Carbon dioxide is a commonly employed irritant test compound in nasal chemesthetic studies because it is essentially free of olfactory stimulus properties. CO₂ is thought to act via hydration to H₂CO₃ and dissociation to H+ in nasal mucus, with resulting activation of acid sensors. However, transient changes in nasal mucosal pH have not been documented during CO₂ stimulation in humans. We placed a small pH probe on the floor of the right anterior nasal cavity during CO₂ stimulation in eight human subjects with historically high (>30%) and low (≤20%) CO₂ detection thresholds. Three second pulses of CO₂ (15-45% v/v) paired with air in random order (12-15 s inter-stimulus interval; 60 s inter-trial interval) were administered by nasal cannula at 5 l/min. in an ascending series. For each subject, both a CO₂ detection threshold and suprathreshold psychophysical ratings [Ψ; labeled magnitude scale] were generated. All subjects showed phasic drops in pH associated with CO₂ stimulation (ΔpH). For all subjects combined, a positive correlation was apparent between applied [CO₂] and both ΔpH and Ψ, as well as between ΔpH and Ψ themselves (P < 0.0001 for each comparison). Subjects with historically low CO₂ thresholds showed steeper dose-response curves for Ψ as a function of both applied [CO₂] and ΔpH, but not for ΔpH as a function of applied [CO₂]. For the six of eight subjects with measurable pH changes at threshold, ΔpH was positively related to log [CO₂ threshold] (P < 0.01). These data imply that variability in CO₂ detection thresholds and suprathreshold rating may derive from intrinsic differences in neural sensitivity, rather than differences in stimulus activation to hydrogen ion.