Thermo sensitive TRPM8 channel and its role in cold induced airway symptoms

Jana Plevkova, Zuzana Biringerova, Silvia Gavliakova

.
Department of Pathological Physiology, JFM CU, Martin, Slovakia.

DOI: 10.4236/ojmip.2012.21004                

Abstract

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 hyper-tonicity 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.

Keywords

Cold Air; Airways; Thermo Sensation; TRPM8; Cold; Hypertonicity

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Cruzz, A.A. and Togias, A. (2008) Upper airway reaction to cold air. Current allergy and asthma reports, 8, 111-117. doi:10.1007/s11882-008-0020-z
[2]	Koskela, H.O. (2007) Cold air provoked respiratory symptoms: The mechanism and management. International Journal of Circumpolar Health, 66,
[3]	Kotaru, C., Hejal, B.R., Finigian, J.H., Coreno, A.J., Skowronski, M.E., Brians, L.J. and McFadden, E.R. (2002) Influence of hyperpnoea on airway surface fluid volume and osmolarity in normal humans. Journal of Applied Physiology, 93, 154-160.
[4]	Giesbrecht, G.G. and Younes, M. (1995) Exercise and cold induced asthma. Canadian Journal of Applied Physiology, 20, 300-314. doi:10.1139/h95-023
[5]	Merre, C.L., Isber, J., Chediak, A.D. and Wunner, A. (2003) Effects of cold dry air nasal stimulation on airway mucosal blood flow in humans. Archives of Physiology and Biochemistry, 2003, 111, 327-329. doi:10.1080/13813450312331337513
[6]	Koskela, H. and Tukiainen, H. (1995) Facial cooling, but not nasal breathing of cold air, induces bronchoconstriction: A study in asthmatic and healthy subjects. European Respiratory Journal, 8, 2088-2093. doi:10.1183/09031936.95.08122088
[7]	Guyton, A.G. and Hull, J.E. (1996) Medical Physiology. 9th Edition, W.B. Saunders, Co., Philadelphia.
[8]	Daviskas, E., Gonda, I. and Anderson, S.D. (1990) Mathematical modelling of heat and water transport in human respiratory tract. Journal of Applied Physiology, 69, 362-372.
[9]	Bessac, B.F. and Jordt, S.E. (2008) Breathtaking TRP channels: TRPA1 and TRPV1 in airway chemosensation and reflex control. Physiology, 23, 360-370. doi:10.1152/physiol.00026.2008
[10]	McFadden, E.R. Jr., Pichurko, B.M., Bowman, H.F., Ingenito, E., Burns, S. and Dowling, N. (1985) Thermal mapping of the airways in humans. Journal of Applied Physiology, 58, 564-570.
[11]	McKemy, D.D. (2005) How cold is it? TRPM8 and TRPA1 in the molecular logic of cold sensation. Molecular Pain, 1. doi:10.1186/1744-8069-1-16
[12]	Xing, H., Ling, X.J., Chen, M., Johnson, R.D., et al. (2008) TRPM8 mechanisms of autonomic nerve response to cold in respiratory airways. Molecular Pain, 4, doi:10.1186/1744-8069-4-22
[13]	Gerhold, K. and Bautista, D.M. (2008) TRPA1: Irritant receptor of the airways. Journal of Physiology, 586, 3303.
[14]	Koskela, H.O., Koskela, A.K. and Tukiainen, H.O. (1996) Bronchoconstriction due to cold weather in COPD. The roles of direct airway effects and cutaneous reflex mechanisms. Chest, 110, 632-636. doi:10.1378/chest.110.3.632
[15]	Johansson, A., Bende, M., Millqvist, E. and Bake, B. (2000) Nasobronchial relationship after cold air provocation. Respiratory Medicine, 94, 1119-1122. doi:10.1053/rmed.2000.0924
[16]	Fontanari, P., Burnet, H., Zattara-Hartmann, M.C. and Jammes, Y. (1996) Changes in airway resistance induced by nasal inhalation of cold dry, dry, or moist air in nor mal individuals. Journal of Applied Physiology, 81, 1739-1743.
[17]	Plevkova, J. and Tatar, M. (2002) Fyziológia a patofyziológia nosovej dutiny, nazálna reaktivita. Cs Physiol, 51, 28-36.
[18]	Togias, A.G., Naclerio, R.M., Proud, D., Fish, J.E., Adkinson, N.F. Jr. and Kagey-Sobotka, A. (1985) Nasal challenge with cold, dry air results in release of inflammatory mediators. The Journal of Clinical Investigation, 76, 1375-1381. doi:10.1172/JCI112113
[19]	Cho, Y.S., Park, S.Y., Lee, C.K., Lee, E.Y., Shin, J.H. and Yoo, B. (2003) Enhanced cough response to hyperpnoea with cold air challenge in chronic cough patients showing increased cough sensitivity to inhaled capsaicin. Allergy, 58, 486-491. doi:10.1034/j.1398-9995.2003.00183.x
[20]	Rundell, K.W., Spiering, B.A., Baumann, J.M. and Evans, T.M. (2005) Effects of montelukast on airway narrowing from eucapnic voluntary hyperventilation and cold air exercise. British Journal of Sports Medicine, 39, 232-236. doi:10.1136/bjsm.2004.014282
[21]	Cruz, A.A., Naclerio, R.M., Proud, D. and Togias, A. (2006) Epithelial shedding is associated with nasal reactions to cold, dry air. The Journal of Allergy and Clinical Immunology, 117, 1351-1358. doi:10.1016/j.jaci.2006.01.054
[22]	Davis, M.S. and Freed, A.N. (2001) Repeated hyperventilation causes peripheral airway inflammation, hyperreactivity and impaired bronchodilatation in dogs. American Journal of Respiratory Critical Care Medicine, 164, 785-789.
[23]	Bonsignore, M.R., Morici, G., Vignola, A.M., Riccobono, L., Bonanno, A. and Profita, M. (2003) Increased airway inflammatory cells in endurance athletes: What do they mean? Clinical Experiment Allergy, 33, 14-21. doi:10.1046/j.1365-2222.2003.01557.x