Sensory properties of citric acid: Psychophysical evidence for sensitization, self-desensitization, cross-desensitization and cross-stimulus-induced recovery following capsaicin

In a first experiment, human subjects used a bipolar scale to rate the irri tant sensation elicited by 10 sequentially repeated applications of either 3 ppm capsaicin or 250 mM citric acid on one side of the dorsal surface of the tongue, at 1 min intervals (30 s inter-stimulus interval). Citric acid- evoked irritation significantly increased across trials, consistent with se nsitization. With capsaicin there was a large degree of inter- and intra-in dividual Variation in successive ratings with no overall sensitization. Fol lowing the sequential stimulation series and a 10 min rest period, self- an d cross-desensitization effects were tested in a two-alternative forced cho ice (2-AFC) paradigm by placing either citric acid or capsaicin on both sid es of the tongue and asking subjects to indicate which side of the tongue y ielded a stronger irritant sensation. Subjects also gave separate intensity ratings for irritation on each side of the tongue. Capsaicin self-desensit ization was confirmed, while cross-desensitization to citric acid was not o bserved. In addition, citric acid self-desensitization and cross-desensitiz ation to capsaicin were observed. In a second experiment a stronger capsaic in solution (33 ppm) was applied to one side of the tongue using cotton swa bs. After the burning sensation elicited by capsaicin had disappeared, citr ic acid was applied bilaterally and cross-desensitization was observed usin g the same 2-AFC and rating procedures. This was followed by repeated re-ap plication of citric acid at 1 min intervals to the capsaicin-treated side. The irritant sensation elicited by citric acid increased significantly, ind icating a 'cross-stimulus-induced recovery' from capsaicin desensitization. In a final experiment we investigated the effect of the sodium channel blo cker amiloride on the perceived irritation elicited by citric acid or capsa icin. Following application of amiloride to one side of the tongue with cot ton swabs, either citric acid or capsaicin was applied bilaterally and subj ects asked to perform a 2-AFC and intensity ratings. Amiloride significantl y, albeit weakly, reduced the irritation elicited by citric acid while it w eakly but significantly enhanced capsaicin-evoked irritation. These finding s are discussed in terms of involvement of vanilloid and acid-sensitive ion channels in acid-evoked irritation and pain.