Cineole, Thymol and Camphor Nasal Challenges and their Effect on Nasal Symptoms and Cough in an Animal Model

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Abstract

Inhalation of aromatic vapours suppressed coughing induced by citric acid (CA) in naive animals. No data are available about their effects in an animal model with primarily up-regulated cough reflex. New data indicate that aromatic vapours suppress cough via effect on nasal sensory nerves.

The aim of our study was to ascertain the efficacy of nasal application of 1,8-cineole, thymol and camphor on nasal symptoms and CA induced cough in validated model of up-regulated cough reflex. Guinea pigs (n=13) were sensitized by intraperitoneal administration of ovalbumin (OVA) and sensitization was confirmed 21 days later by skin tests. Sensitized animals were repeatedly challenged with nasal OVA to induce rhinitis, and further experiments (cough challenges) were performed during the early phase of allergic inflammation.

Cough was induced by CA in plethysmograph for 10 minutes after nasal pre-treatment with aromatic substances (10-3M) in rhinitis model. Cough was recognized from record of sudden airflow changes interrupting breathing pattern and cough sound. Final count of coughs was established by blind analysis using SonicVisualiser Software. Dose responses curves, total cough count and cough latency were analyzed.

Repeated intranasal challenge with OVA induces progressively worsening symptoms, and cough induced by CA during acute phase of allergic rhinitis was enhanced. Nasal pre-treatment with 1,8-cineole, thymol and camphor did not prevent onset of nasal symptoms, and the magnitude of symptoms was comparable to those without pretreatment. Camphor had the most potent antitussive effects (number of coughs 25±3 vs. 7±2, p<0.05) followed by thymol (number of coughs 25±3 vs. 14±2, p<0.05). The data for nasal 1,8-cineole challenge did not reach statistical significance. Cough latency followed this trend.

Although the magnitude of nasal symptoms is not influenced, the effect on cough is in case of camphor and thymol significant. Our data showed that nasal application of aromatic substances suppress citric acid induced cough in animals with up-regulated cough reflex.

References
  • 1. Kreindler JL, Chen B, Kreitman Y, Kofonow J, Adams K, Cohen NA. The novel dry extract BNO 1011 stimulates chloride transport and ciliary beat frequency in human respiratory epithelial cultures. Am J Rhinol and Allergy 2012; 26 (6): 439-443.

  • 2. Kemmerich B, Eberhardt B, Stammer H. Efficacy and tolerability of a fluid extract combination of the thyme herb and ivy leaves and matched placebo in adults suffering from acute bronchitis with productive cough. Arzneim-Forsch/Drug Research 2006; 56 (9): 652-660.

  • 3. Jund R, Mondilger M, Steindl H, Stammer H, Stierna P, Bachert C. Clinical efficacy of a dry exracts of five herbal drugs in acute viral rhinosinusitis. Rhinology 2012; 50: 417-426.

  • 4. Glatthaar-Saalmuller B, Rauchhaus U, Rode S, Haunschild J, Saalmuller A. Antiviral activity in vitro of two preparation of the herbal medicinal product Sinupret against viruses causing respiratory infection.\ Phytomedicine 2011; 19: 1-7.

  • 5. Rossi A, Dehm F, Kiesselbach Ch, Haunschild J. The novel Sinupret dry extract exhibits anti-inflammatory effectiveness in vivo. Fitoterapia 2012; 83: 715-720.

  • 6. Laude EA, Morice AH, Grattan TJ. The antitussive effects of menthol, camphor and cineole in conscious GP. Pulm Pharmacol 1994; 7 (3): 179-184.

  • 7. Gavliakova S, Biringerova Z, Buday T, Brozmanova M, Calkovsky V, Poliacek I, Plevkova J. Antitussive effects of nasal thymol challenges in healthy volunteers. Respir Physiol Neurobiol. 2013; 187(1):104-7.

  • 8. Plevkova J, Kollarik M, Poliacek I, Brozmanova M, Surdenikova L, Tatar M, Mori N, Canning BJ. The role of trigeminal nasal TRPM8-expressing afferent neurons in the antitussive effects of menthol. J Appl Physiol 2013; 115(2): 268-74.

  • 9. Buday T, Brozmanova M, Biringerova Z, Gavliakova S, Poliacek I, Calkovsky V, Shetthalli MV, Plevkova J. Modulation of cough response by sensory inputs from the nose - role of trigeminal TRPA1 versus TRPM8 channels. Cough 2012; 3(1):11 -18

  • 10. McKemy DD How cold is it? TRPM8 and TRPA1 in molecular logic of cold sensation. Mol Pain 2005; 1:16.doi:10.1186/1744-8069

  • 11. Kobayashi K, Fukuoka T, Obata K, Yamanaka H, Dai Y, Tokunaga A, Noguchi K. Distinct expression of TRPM8, TRPA1 a TRPV1 m RNA in rat primary afferent neuron with Ad/C fibers and colocalization with trk receptors. J Comp Neurol 2005; 493: 596-606.

  • 12. Abe J, Hosakawa H, Okazawa M. TRPM8 protein localisation in trigeminal ganglia and taste papillae. Molecular Brain Research 2005; 136 (2) 91-98.

  • 13. Xu H, Ramsey IS, Kotecha SA, Moran MM, Chong JA, Lawson D, Ge P, Lilly J, Silos-Santiago I, Xie Y, DiStefano PS, Curtis R, Clapham DE. TRPV3 is a calcium-permeable temperature-sensitive cation channel. Nature 2002; 418(6894): 181-186.

  • 14. Xu H, Blair NT, Clapham DE. Camphor activates and strongly desensitizes the transient receptor potential vanilloid subtype 1 channel in a vanilloid-independent mechanism. J Neurosci 2005, 25(39):8924-8937.

  • 15. Morice AH, Geppetti P. Cough. 5: The type 1 vanilloid receptor: a sensory receptor for cough. Thorax 2004; 59(3):257-258.

  • 16. Plevkova J, Kollarik M, Brozmanova M, Revallo M, Varechova S, Tatar M. Modulation of experimentally-induced cough by stimulation of nasal mucosa in cats and guinea pigs Respir Physiol Neurobiol 2004; 142: 225-235.

  • 17. Canning BJ, Mori N. Encoding of the cough reflex in anaesthetized guinea pigs. Am J Physiol Regul Integr Comp Physiol 2011; 300(2):369-377.

  • 18. Brozmanova M, Plevkova J, Tatar M, Kollarik M. Cough reflex sensitivity is increased in the guinea pig model of allergic rhinitis. Journal of physiology and pharmacology 2008; 59 (6):153-161.

  • 19. Underwood S, Foster M, Raeburn D, Bottoms S, Karlsson JA. Time-course of antigen-induced airway inflammation in the guinea-pig and its relationship to airway hyperresponsiveness. Eur Respir J 1995; 8(12):2104-13.

  • 20. Galeotti N, Di Cesare Mannelli L, Mazzanti G, Bartolini A, Ghelardini C. Menthol: a natural analgesic compound. Neurosci Lett 2002; 322(3):145-8.

  • 21. R. Eccles. Menthol: effects on nasal sensation of airflow and the drive to breathe. Curr Allergy Asthma Rep 2003; 3: 210-214

  • 22. Millqvist E, Ternesten-Hasséus E, Bende M. Inhalation of menthol reduces capsaicin cough sensitivity and influences inspiratory flows in chronic cough. Respiratory Medicine 2013; 107 (3): 433-438

  • 23. T Nabe, N. Mizutani, K. Shimizu, H. Takenaka, S. Kohno. Development of pollen-induced allergic rhinitis with early and late phase nasal blockage in guinea pigs Inflammation Research 1998; 47 (9): 369-374

  • 24. Tatar M, Sant’Ambrogio G, Sant’Ambrogio F B. Laryngeal and tracheobronchial cough in anesthetized dogs. J Appl Physiol 1994; 76 (6): 2672-9.

  • 25. Ricciardolo FL, Rado V, Fabbri LM, Sterk PJ, DiMaria GU, Geppetti P. Bronchoconstriction induced by citric acid inhalation in guinea pigs: role of tachykinins, bradykinin, and nitric oxide. Am J Respir Crit Care Med 1999; 159 (2): 557-62.

  • 26. Biringerova Z, Gavliakova S, Brozmanova M, Tatar M, Hanuskova E, Poliacek I, Plevkova J. The effects of nasal irritant induced responses on breathing and cough in anaesthetized and conscious animal models. Respir Physiol Neurobiol 2013; doi:pii: S1569-9048(13)00274-7. 10.1016/j.resp.2013.08.003.

  • 27. Poussel M, Varechova S, Demoulin B, Chalon B, Schweitzer C, Marchal F, Chenuel B Nasal stimulation by water down-regulates cough in anesthetized rabbits. Respir Physiol Neurobiol 2012; 183(1):20-25.

  • 28. Tatar M, Nagyova B. Abdominal capsaicin-sensitive receptor activation and mechanically induced cough in anesthetized cats. International Union of Physiological Science, Prague 1991 (98).

  • 29. Tatar M, Nagyova B, Widdicombe JG. Veratrine-induced reflexes and cough. Respir Med 1991; 85(A): 51-55.

  • 30. Widdicombe J, Eccles R, Fontana G. Supramedullary influences on cough. Respir Physiol Neurobiol 2006, 52(3):320-328.

  • 31. Van den Bergh O, Van Diest I, Dupont L, Davenport PW. On the Psychology of Cough. Lung 2011.

  • 32. Keh SM, Facer P, Yehia A, Sandhu G, Saleh HA, Anand P. The menthol and cold sensation receptor TRPM8 in normal human nasal mucosa and rhinitis. Rhinology. 2011; 49(4):453-7.

  • 33. Desesa CR, Vaughan RP, Lanosa MJ, Fontaine KG, Morris JB. Sulfur-containing malodorant vapours enhance responsiveness to the sensory irritant capsaicin. Toxicol Sci 2008;104(1):198-209.

  • 34. Jurecek L, Nosalova G, Hromadkova Z, Kostalova Z. Antitussive activity of extracts from Fallopia Sachalinenesis. Acta Medica Martiniana 2012, Suppl. 1, 24-30.

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The Journal of Comenius University in Bratislava

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