Restor Dent Endod.  2016 Aug;41(3):202-209. 10.5395/rde.2016.41.3.202.

Involvement of TRPA1 in the cinnamaldehyde-induced pulpal blood flow change in the feline dental pulp

Affiliations
  • 1Department of Conservative Dentistry, Kyungpook National University School of Dentistry, Daegu, Korea. skykim@knu.ac.kr

Abstract


OBJECTIVES
The purpose of this study was to investigate the involvement of TRPA1 in the cinnamaldehyde-induced pulpal blood flow (PBF) change in the feline dental pulp.
MATERIALS AND METHODS
Mandibles of eight cats were immobilized and PBF was monitored with a laser Doppler flowmetry at the mandibular canine tooth. To evaluate the effect of cinnamaldehyde on PBF, cinnamaldehyde was injected into the pulp through the lingual artery at a constant rate for 60 seconds. As a control, a mixture of 70% ethanol and 30% dimethyl sulfoxide (DMSO, vehicle) was used. To evaluate the involvement of transient receptor potential ankyrin 1 (TRPA1) in PBF change, AP18, a specific TRPA1 antagonist, was applied into the pulp through the Class V dentinal cavity followed by cinnamaldehyde-administration 3 minutes later. The paired variables of experimental data were statistically analyzed using paired t-test. A p value of less than 0.05 was considered as statistically significant.
RESULTS
Administration of cinnamaldehyde (0.5 mg/kg, intra-arterial [i.a.]) induced significant increases in PBF (p < 0.05). While administration of a TRPA1 antagonist, AP18 (2.5 - 3.0 mM, into the dentinal cavity [i.c.]) caused insignificant change of PBF (p > 0.05), administration of cinnamaldehyde (0.5 mg/kg, i.a.) following the application of AP18 (2.5 - 3.0 mM, i.c.) resulted in an attenuation of PBF increase from the control level (p < 0.05). As a result, a TRPA1 antagonist, AP18 effectively inhibited the vasodilative effect of cinnamaldehyde (p < 0.05).
CONCLUSIONS
The result of the present study provided a functional evidence that TRPA1 is involved in the mechanism of cinnamaldehyde-induced vasodilation in the feline dental pulp.

Keyword

Blood flow; Cinnamaldehyde; Dental pulp; TRPA1

MeSH Terms

Animals
Ankyrins
Arteries
Cats
Cuspid
Dental Pulp*
Dentin
Dimethyl Sulfoxide
Ethanol
Laser-Doppler Flowmetry
Mandible
Vasodilation
Ankyrins
Dimethyl Sulfoxide
Ethanol

Figure

  • Figure 1 Schematic diagram of experiment design. Pulpal blood flow was measured at tooth surface by a laser Doppler flowmeter. Femoral artery was cannulated for monitoring of systemic blood pressure and femoral vein was cannulated for injection of supplemental anesthetics. TRPA1 antagonist was administered through the dentinal cavity and cinnamaldehyde was injected into the pulp through the lingual artery. TRPA1, transient receptor potential ankyrin 1.

  • Figure 2 Typical strip-chart recordings of systemic blood pressure and pulpal blood flow (PBF). (a) Cinnamaldehyde (0.5 mg/kg, i.a.) resulted in a significant increase of PBF; (b) TRPA1 antagonist, AP18 (2.5 - 3.0 mM, i.c.), effectively attenuated an increase in PBF induced by cinnamaldehyde (0.5 mg/kg, i.a.) (p < 0.05). i.a., intra-arterial; i.c., into the dentinal cavity.


Reference

1. Hargreaves KM, Cohen S, Berman LH. Cohen's pathways of pulp. 10th ed. St. Louis: Mosby Elsevier;2011. p. 571.
2. Heyeraas KJ, Kim S, Raab WH, Byers MR, Liu M. Effect of electrical tooth stimulation on blood flow, interstitial fluid pressure and substance P and CGRP-immunoreactive nerve fibers in the low compliant cat dental pulp. Microvasc Res. 1994; 47:329–343.
Article
3. Nyman E, Franzén B, Nolting A, Klement G, Liu G, Nilsson M, Rosén A, Björk C, Weigelt D, Wollberg P, Karila P, Raboisson P. In vitro pharmacological characterization of a novel TRPA1 antagonist and proof of mechanism in a human dental pulp model. J Pain Res. 2013; 6:59–70.
4. Kobayashi K, Fukuoka T, Obata K, Yamanaka H, Dai Y, Tokunaga A, Noguchi K. Distinct expression of TRPM8, TRPA1, and TRPV1 mRNAs in rat primary afferent neurons with delta/c-fibers and colocalization with trk receptors. J Comp Neurol. 2005; 493:596–606.
Article
5. Salas MM, Hargreaves KM, Akopian AN. TRPA1-mediated responses in trigeminal sensory neurons: interaction between TRPA1 and TRPV1. Eur J Neurosci. 2009; 29:1568–1578.
Article
6. El Karim IA, Linden GJ, Curtis TM, About I, McGahon MK, Irwin CR, Killough SA, Lundy FT. Human dental pulp fibroblasts express the 'cold-sensing' transient receptor potential channels TRPA1 and TRPM8. J Endod. 2011; 37:473–478.
Article
7. Nilius B, Appendino G, Owsianik G. The transient receptor potential channel TRPA1: from gene to pathophysiology. Pflugers Arch. 2012; 464:425–458.
Article
8. Radresa O, Dahllof H, Nyman E, Nolting A, Albert JS, Raboisson P. Roles of TRPA1 in pain pathophysiology and implications for the development of a new class of analgesic drugs. Open Pain J. 2013; 6:137–153.
Article
9. Story GM, Peier AM, Reeve AJ, Eid SR, Mosbacher J, Hricik TR, Earley TJ, Hergarden AC, Andersson DA, Hwang SW, McIntyre P, Jegla T, Bevan S, Patapoutian A. ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures. Cell. 2003; 112:819–829.
Article
10. Jordt SE, Bautista DM, Chuang HH, McKemy DD, Zygmunt PM, Högestätt ED, Meng ID, Julius D. Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1. Nature. 2004; 427:260–265.
Article
11. Bandell M, Story GM, Hwang SW, Viswanath V, Eid SR, Petrus MJ, Earley TJ, Patapoutian A. Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin. Neuron. 2004; 41:849–857.
Article
12. Xue YL, Shi HX, Murad F, Bian K. Vasodilatory effects of cinnamaldehyde and its mechanism of action in the rat aorta. Vasc Health Risk Manag. 2011; 7:273–280.
13. Aneja KR, Joshi R, Sharma C. Antimicrobial activity of Dalchini (Cinnamomum zeylanicum bark) extracts on some dental caries pathogens. J Pharm Res. 2009; 2:1387–1390.
14. Gupta C, Kumari A, Garg AP, Catanzaro R, Marotta F. Comparative study of cinnamon oil and clove oil on some oral microbiota. Acta Biomed. 2011; 82:197–199.
15. Silva CR, Oliveira SM, Rossato MF, Dalmolin GD, Guerra GP, da Silveira Prudente A, Cabrini DA, Otuki MF, André E, Ferreira J. The involvement of TRPA1 channel activation in the inflammatory response evoked by topical application of cinnamaldehyde to mice. Life Sci. 2011; 88:1077–1087.
Article
16. Liu MT, Bioltto G, Markowitz K, Kim S. Changes in coronal pulpal blood flow following a class V cavity preparation. J Dent Res. 1987; 66:Supplment 1. Abstract #558. 76.
17. Kim SK, Ang L, Hsu YY, Dörcher-Kim J, Kim S. Antagonistic effect of D-myo-inositol-1,2,6-trisphosphate (PP56) on neuropeptide Y-induced vasoconstriction in the feline dental pulp. Arch Oral Biol. 1996; 41:791–798.
Article
18. Taylor-Clark TE, McAlexander MA, Nassenstein C, Sheardown SA, Wilson S, Thornton J, Carr MJ, Undem BJ. Relative contributions of TRPA1 and TRPV1 channels in the activation of vagal bronchopulmonary C-fibres by the endogenous autacoid 4-oxononenal. J Physiol. 2008; 586:3447–3459.
Article
19. Bessac BF, Sivula M, von Hehn CA, Escalera J, Cohn L, Jordt SE. TRPA1 is a major oxidant sensor in murine airway sensory neurons. J Clin Invest. 2008; 118:1899–1910.
Article
20. Karashima Y, Talavera K, Everaerts W, Janssens A, Kwan KY, Vennekens R, Nilius B, Voets T. TRPA1 acts as a cold sensor in vitro and in vivo. Proc Natl Acad Sci USA. 2009; 106:1273–1278.
21. Macpherson LJ, Xiao B, Kwan KY, Petrus MJ, Dubin AE, Hwang S, Cravatt B, Corey DP, Patapoutian A. An ion channel essential for sensing chemical damage. J Neurosci. 2007; 27:11412–11415.
Article
22. Trevisani M, Siemens J, Materazzi S, Bautista DM, Nassini R, Campi B, Imamachi N, Andrè E, Patacchini R, Cottrell GS, Gatti R, Basbaum AI, Bunnett NW, Julius D, Geppetti P. 4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1. Proc Natl Acad Sci USA. 2007; 104:13519–13524.
Article
23. Pozsgai G, Bodkin JV, Graepel R, Bevan S, Andersson DA, Brain SD. Evidence for the pathophysiological relevance of TRPA1 receptors in the cardiovascular system in vivo. Cardiovasc Res. 2010; 87:760–768.
Article
24. Yanaga A, Goto H, Nakagawa T, Hikiami H, Shibahara N, Shimada Y. Cinnamaldehyde induces endothelium-dependent and -independent vasorelaxant action on isolated rat aorta. Biol Pharm Bull. 2006; 29:2415–2418.
Article
25. Earley S. TRPA1 channels in the vasculature. Br J Pharmacol. 2012; 167:13–22.
Article
26. Kunkler PE, Ballard CJ, Oxford GS, Hurley JH. TRPA1 receptors mediate environmental irritant-induced meningeal vasodilatation. Pain. 2011; 152:38–44.
Article
27. Bautista DM, Jordt SE, Nikai T, Tsuruda PR, Read AJ, Poblete J, Yamoah EN, Basbaum AI, Julius D. TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents. Cell. 2006; 124:1269–1282.
Article
28. Högestätt ED, Johansson R, Andersson DA, Zygmunt PM. Involvement of sensory nerves in vasodilator responses to acetylcholine and potassium ions in rat hepatic artery. Br J Pharmacol. 2000; 130:27–32.
Article
29. Harada M, Ozaki Y. Pharmacological studies on Chinese cinnamon. I. Central effects of cinnamaldehyde. Yakugaku Zasshi. 1972; 92:135–140.
Article
30. Guo JY, Huo HR, Zhao BS, Liu HB, Li LF, Ma YY, Guo SY, Jiang TL. Cinnamaldehyde reduces IL-1beta-induced cyclooxygenase-2 activity in rat cerebral microvascular endothelial cells. Eur J Pharmacol. 2006; 537:174–180.
Article
31. Chang ST, Chen PF, Chang SC. Antibacterial activity of leaf essential oils and their constituents from Cinnamomum osmophloeum. J Ethnopharmacol. 2001; 77:123–127.
Article
32. Takenaga M, Hirai A, Terano T, Tamura Y, Kitagawa H, Yoshida S. In vitro effect of cinnamic aldehyde, a main component of Cinnamomi Cortex, on human platelet aggregation and arachidonic acid metabolism. J Pharmacobiodyn. 1987; 10:201–208.
Article
33. Huang J, Wang S, Luo X, Xie Y, Shi X. Cinnamaldehyde reduction of platelet aggregation and thrombosis in rodents. Thromb Res. 2007; 119:337–342.
Article
34. Huang CC, Won HT, Cheng JK, Chen CC, Hung YC. Cinnamaldehyde prolongs cutaneous analgesia of local anesthetics in rats. Anesthesiology 2011. In : American Society of Anesthesiologists Annual Meeting (Regional anesthesia and acute pain; p. Abstract #A991. updated 2016 Jul 29. Available from: http://www.asaabstracts.com/strands/asaabstracts/abstractList.htm;jsessionid=43A31BC5F56A2DDB2462F253453561B4?year=2011&index=17.
35. Boonen B, Alpizar YA, Benoy V, Van den Bosch L, Voets T, Talavera K. The Trpa1 agonist cinnamaldehyde acts as a local anesthetic inhibiting voltage-gated sodium channels in sensory neurons. Biophys J. 2014; 106:326a–327a.
Article
36. Markowitz K, Moynihan M, Liu M, Kim S. Biologic properties of eugenol and zinc oxide-eugenol. A clinically oriented review. Oral Surg Oral Med Oral Pathol. 1992; 73:729–737.
37. Klein AH, Carstens MI, Zanotto KL, Sawyer CM, Ivanov M, Cheung S, Carstens E. Self- and cross-desensitization of oral irritation by menthol and cinnamaldehyde (CA) via peripheral interactions at trigeminal sensory neurons. Chem Senses. 2011; 36:199–208.
Article
38. Cocchiara J, Letizia CS, Lalko J, Lapczynski A, Api AM. Fragrance material review on cinnamaldehyde. Food Chem Toxicol. 2005; 43:867–923.
Article
39. Macpherson LJ, Dubin AE, Evans MJ, Marr F, Schultz PG, Cravatt BF, Patapoutian A. Noxious compounds activate TRPA1 ion channels through covalent modification of cysteines. Nature. 2007; 445:541–545.
Article
40. Defalco J, Steiger D, Gustafson A, Emerling DE, Kelly MG, Duncton MA. Oxime derivatives related to AP18: agonists and antagonists of the TRPA1 receptor. Bioorg Med Chem Lett. 2010; 20:276–279.
Article
41. Stucky CL, Dubin AE, Jeske NA, Malin SA, McKemy DD, Story GM. Roles of transient receptor potential channels in pain. Brain Res Rev. 2009; 60:2–23.
Article
42. Petrus M, Peier AM, Bandell M, Hwang SW, Huynh T, Olney N, Jegla T, Patapoutian A. A role of TRPA1 in mechanical hyperalgesia is revealed by pharmacological inhibition. Mol Pain. 2007; 3:40.
Article
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