BackgroundCough, the most important airways defensive mechanism is modulated by many afferent inputs either from respiratory tussigenic areas, but also by afferent drive from other organs. In animal models, modulation of cough by nasal afferent inputs can either facilitate or inhibit the cough response, depending on the type of trigeminal afferents stimulated.MethodsIn this study we addressed the question of possible bidirectional modulation of cough response in human healthy volunteers by nasal challenges with TRPA1 and TRPM8 agonists respectively. After nasal challenges with isocyanate (AITC), cinnamaldehyde, (−) menthol and (+) menthol (all 10-3 M) nasal symptom score, cough threshold (C2), urge to cough (Cu) and cumulative cough response were measured).ResultsNasal challenges with TRPA1 relevant agonists induced considerable nasal symptoms, significantly enhanced urge to cough (p<0.05) but no statistically significant modulation of the C2 and cumulative cough response. In contrast, both TRPM8 agonists administered to the nose significantly modulated all parameters including C2 (p<0.05), Cu (p<0.01) and cumulative cough response (p <0.01) documenting strong anti irritating potential of menthol isomers.ConclusionsIn addition to trigeminal afferents expressing TRP channels, olfactory nerve endings, trigemino – olfactoric relationships, the smell perception process and other supramedullar influences should be considered as potential modulators of the cough response in humans.

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It is generally accepted that environmental factors can significantly influence respiratory system. Cold is one of these factors. Understanding of the reaction of airways to cold air is very important tool leading to improvement in management of cold induced rhinitis, cold induced asthma, exercise induced asthma, and exacerbation of chronic airway diseases induced by cold exposure. Despite the airways are protected against cold air by powerful heat and moisture exchanging counter current system within the nose, they are still at the risk of onset and development of cold induced symptoms mainly if this mechanism is insufficient, exposed person hyperventilates or is breathing subfreezing air. Some of the mechanisms involved in cold air induced reactions are understood quite well, but some of them are still discussed as they have not been satisfactorily explained, yet. Most discussed mechanisms by which cold air may induce respiratory symptoms include direct cooling and exsiccation of mucosal surface with subsequent hypertonicity of superficial fluid layer and interactions between the trigeminal and the vagus nerve at the central level. Molecular background for such a reaction may rely on the presence of thermo sensitive channels, mainly TRPM8, expressed on airway afferent nerves, which initiate response to cold air, giving a rise to autonomic responses like bronchoconstriction, cough, dyspnoea, chest tightness, mucus secretion and mucosal swelling. Identification of targets for cold action in the airway may help to identify potent antagonists which may prevent or reverse cold induced reactions sharing possibility for clinical application.

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Plevkova et al.: The role of nasal trigeminal nerves expressing TRP channels in modulation of cough threshold and urge to coughpossible clinical application. Clinical and Translational Allergy 2013 3(Suppl 2):O17.