Ibuprofen as a chemesthetic stimulus: Evidence of a novel mechanism of throat irritation

This paper reports a study of the oral and pharyngeal chemesthetic effects of the non-steroidal anti-inflammatory drug (NSAID) ibuprofen [2-(4-isobuty lphenyl)propanoic acid], which pilot experiments had indicated produces an unusual sensory irritation of the throat. In experiment I subjects swallowe d aqueous solutions of ibuprofen prepared with different buffering agents a nd gave ratings of irritation and taste in the mouth and throat. The result s showed that ibuprofen irritates the throat much more than the mouth, and that its quality in the throat is characterized primarily as sting/prick, i tch and tickle (often leading to cough). Based upon the results obtained wi th the different buffering agents, we hypothesized that the sting/prick/itc h qualities of throat irritation were pH-dependent. Parametric manipulation of solution pH in experiment 2 confirmed this hypothesis. The same experim ent revealed that, in contrast to other oral irritants (e.g. capsaicin and menthol), repeated stimulation caused neither sensitization nor desensitiza tion of throat irritation. In the final experiment we found that ibuprofen' s throat irritation could not be modulated by temperature, as it should be if stimulation occurred via capsaicin-sensitive receptors. We therefore con clude that ibuprofen has novel chemesthetic properties, which are not media ted by capsaicin-sensitive (vanilloid) receptors, and that a major componen t of the throat irritation it produces occurs via a pH-dependent receptor m echanism.