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Modulation of cough response by sensory inputs from the nose - role of trigeminal TRPA1 versus TRPM8 channels

Tomas Buday1, Mariana Brozmanova1, Zuzana Biringerova12, Silvia Gavliakova1, Ivan Poliacek3, Vladimir Calkovsky4, Manjunath V Shetthalli5 and Jana Plevkova1*

Author Affiliations

1 Department of Pathophysiology, Comenius University, Jessenius Faculty of Medicine Martin, Sklabinska Str. 26, Martin, 036 01, Slovak Republic

2 Clinic of Anaesthesiology and Emergency Medicine, Jessenius Faculty of Medicine and University Hospital, Martin, Slovak Republic

3 Department of Medical Biophysics, Comenius University, Jessenius Faculty of Medicine, Martin, Slovak Republic

4 Clinic of Ear Nose throat Diseases, Head and Neck Surgery, Jessenius Faculty of Medicine and University Hospital, Martin, Slovak Republic

5 Pediatric Department, Royal Gwent Hospital, Newport, Wales, United Kingdom

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Cough 2012, 8:11  doi:10.1186/1745-9974-8-11

Published: 3 December 2012



Cough, 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.


In 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).


Nasal 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.


In 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.

Cough; Nose; Irritants; Menthol; Trigeminal; Olfactory