Factors affecting the sensitivity of the lingual trigeminal nerve to acids

Oral sensitivity to acids mediates a range of irritation, from desirable sensations of pungency in various foods and beverages to the pain associated with harmful levels of acidity and inflammation. To characterize the role of the epithelial and vascular processes in neural sensitivity to acid applied to the lingual mucosa, we measured lingual trigeminal nerve responses in rats to acidic stimuli of varying physicochemical properties. Stimulatory efficacy was strongly correlated with lipophilicity (octanol-H2O partition coefficient) for the series of straight-chain fatty acids from one to six carbons. Neither acid dissociation constant nor the pH of stimulus solutions correlated with stimulatory efficacy for the fatty acids and six other organic acids. The hypothesis that weakly acidic stimuli gain access to trigeminal nerve endings primarily through the lipid phase of the epithelium was supported by these findings. Further support for this hypothesis is the result that LaCl3, an inhibitor of epithelial tight junctions, had no effect on the neural response to n-pentanoic acid. The potential relevance of buffering-clearance in modulating responses to acid was indicated by the finding that the application of 1 mM capsaicin to the tongue reversibly inhibited the neural response to acid, as well as causing plasma extravasation in lingual epithelium.