Real-time Monitoring of Nasal Mucosal pH During Carbon Dioxide Stimulation: Implications for Stimulus Dynamics

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Abstract
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.

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