Browse > Article
http://dx.doi.org/10.5395/JKACD.2004.29.3.239

Local Application of NK1 Receptor Antagonists and Pulpal Blood Flow in Cat  

Kim, Young-Kyung (Department of Conservative Dentistry, School of Dentistry, Kyungpook National University)
Chu, Wan-Sik (Department of Conservative Dentistry, School of Dentistry, Kyungpook National University)
Lee, Ho-Jeong (Department of Oral Physiology, School of Dentistry, Kyungpook National University)
Ahn, Dong-Kuk (Department of Oral Physiology, School of Dentistry, Kyungpook National University)
Yoo, Hyun-Mi (Department of Conservative Dentistry, The Institute of Oral Health Science, Samsung Medical Center, Sungkyunkwan University, School of Medicine)
Kim, Sung-Kyo (Department of Conservative Dentistry, School of Dentistry, Kyungpook National University)
Publication Information
Restorative Dentistry and Endodontics / v.29, no.3, 2004 , pp. 239-248 More about this Journal
Abstract
The purpose of this study was to investigate the influence of NK1 receptor antagonists on the pulpal blood flow (PBF) when applied iontophoretically through the dentinal cavity of the teeth in order to understand whether iontophoretically applied NK1 receptor antagonists can control the pulpal inflammation. Eleven cats were anesthetized with alpha-chloralose and urethane, and substance P (SP) was administered to the dental pulp through the catheterized lingual artery in doses that caused PBF change without the influence of systemic blood pressure. NK1 receptor antagonists were applied iontophoretically to the prepared dentinal cavity of ipsilateral canine teeth of the drug administration, and PBF was monitored. Data were analyzed statistically with paired t-test. PBF increase after iontophoretic application of the NK1 receptor antagonists followed by the intra-arterial administration of SP was significantly less than PBF increase after iontophoretic application of the 0.9% saline followed by the intra-arterial administration of SP as a control (p < 0.05). Iontophoretic application of the NK1 receptor antagonists (0.2~3.4 mM) following the intra-arterial administration of SP resulted in less increase of PBF than the iontophoretic application of the 0.9% saline following the intra-arterial administration of SP as a control (p < 0.05). Therefore. the results of the present study provide evidences that the iontophoretic application is an effective method to deliver drugs to the dental pulp. and that iontophoretically applied NK1 receptor antagonists block SP-induced vasodilation effectively. The above results show the possibility that the iontophoretical application of NK1 receptor antagonists can control the neurogenic inflammation in the dental pulp.
Keywords
NK1 receptor antagonists; SP; Pulpal blood flow; Iontophoresis; Pulpal inflammation; Neurogenic inflammation;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Otsuka M, Yanagisawa M. Does substance P act as a pain transmitter? Trends Pharmacol Sci 8:506 510, 1987   DOI   ScienceOn
2 Berggreen E, Heyeraas KJ. Effect of sensory neuropeptide antagonists h CGRP(8 37) and SR 140.33 on pulpal and gingival blood flow in ferrets. Archs Oral Biol 45:537 542, 2000   DOI   ScienceOn
3 Alia S, Azerad J, Pollin B. Effects of RPR 100893, a potent NKl antagonist, on the jaw opening reflex in the guinea pig. Brain Res 787(1):99 106, 1998   DOI   ScienceOn
4 Wiesenfeld Hallin Z, Villar MJ, Hokfelt T. The effects of intrathecal galanin and C fiber stimulation on the flexor reflex in the rat. Brain Res 486: 205 213, 1989   DOI   ScienceOn
5 Kim S. Regulation of blood flow of the dental pulp: macrocirculation and microcirculation studies (Ph. D. dissertation). New York, NY, Columbia University, 1981
6 Parkhouse N, Lequesne PM. Quantitative objective assessment of peripheral nociceptive C fibre function Neuro Neurosur Psych 51:28 34, 1988   DOI
7 Roderick A, Westerman RA, Widdop RE, Hogan C, Zimmet P. Non invasive tests of neurovascular function: reduced responses in diabetes mellitus. Neurosci Lett 81:177 182, 1987   DOI   PUBMED   ScienceOn
8 Westerman RA, Widdop RE, Hannaford J, Low A, Roberts RGD, Kent P, Sideris K, Yip T, Hales JRS, Stephens FRN. Laser Doppler velocimetry in the mea surement of neurovascular function. Clin Exper Neurol 24:53 66,1988
9 Kim SK, Karabucak B, Welsch H, Simchon S, Kim S. lntracellular mechanism of substance P induced vasodilatation in bovine dental pulp. J Endodont 27:231, 2001
10 von Euler US, Gaddum JH. An unidentified depressor substance in certain tissue extracts. J Physiol (London) 72:74 87, 1931   DOI   PUBMED
11 Henry JL. Substance P and inflammatory pain: potential of substance P antagonists as analgesics. Agent Act Supp 41:75 87, 1993
12 Fazekas A, Gyorfi A, Irmes F, Rosivall L. Effect of substance P administration on vascular permeability in the rat dental pulp and submandibular gland. Proc Finn Dent Soc 88:481 486, 1992
13 Kim SK, Ang L, Hsu YY, Kim S. Characterization of NKl receptor antagonists on pulpal hemodynamics in cats. J Endodont 21(4):229, 1995
14 Foreman JC, Jordan CC. Neurogenic inflammation. Trends Pharmacol Sci 5:116 119, 1984   DOI   ScienceOn
15 Beattie DT, Connor HE, Hagan RM. Recent development in tachykinin NK1 receptor antagonists: prospects for the treatment of migraine headache. Can J Physiol Pharmacol 73:871 877, 1995   DOI   PUBMED   ScienceOn
16 Lindblad LE, Ekenvall L, Ancker K, Rohman H, Oberg PA. Laser Doppler flow meter assessment of ion tophoretically applied norepinephrine on human finger skin circulation. J Inves Dermatol 213:634 636, 1986
17 Wiesenfeld Hallin Z, Xu XJ, Hakanson R, Feng DM, Forker T. The specific antagonistic effect of intrathecal Spantide II on substance P and C fiber conditioning stimulation induced facilitation on the nociceptive flex or reflex in the rat. Brain Res 526:284 290, 1990   DOI   ScienceOn
18 Lembeck F, Folkers K, Donnerer J. Analgesic effect of antagonists of substances. Biochem Biophys Res Commumic 103:1318 1321, 1981   DOI   ScienceOn
19 Buck SH, Burcher E. The tachykinins: a family of peptides with a brood of 'receptors' . Trends Pharmacol Sci 7:65 68, 1986   DOI   ScienceOn
20 Olgart L, Edwall L, Gazelius B. Involvement of affer ent nerves in pulpal blood flow reactions in response to clinical and experimental procedures in the cat. Archs Oral Biol 36:575, 1991   DOI   ScienceOn
21 Lembeck F, Gamse R. Substance P in Peripheral Sensory Processes. Ciba foudation symposium (91):35 54, 1982
22 Kim S, Dorscher Kim JE. Hemodynamic regulation of the dental pulp in a low compliance environment. J Endodont 15(9):404 408, 1989   DOI   ScienceOn
23 Vongsavan N, Matthews B. The permeability of cat dentine in vivo and in vitro. Archs Oral Biol 36:641 646, 1991   DOI   ScienceOn
24 Kim S. Neurovascular interaction in the dental pulp in health and inflammation. J Endodont 16(2):48 53, 1990   DOI   PUBMED   ScienceOn
25 Lembeck F, Holzer P. Substance P as neurogenic mediator of antidromic vasodilation and neurogenic plasma extravasation. Arch Pharmacol 310:175 183, 1979   DOI
26 Kim S, Trowbridge H, Dorscher kim JE. The effects of 5 hydroxytryptamine on pulpal hemodynamics in dogs. J Dent Res 65:682 685, 1986   DOI   PUBMED   ScienceOn
27 Regoli D, Drapeau G, Dion S, Couture R. New selective agonist for neurokinin receptors: pharmacological tools for receptor characterization. Trends Pharmacol Sci 9:290 295, 1988   DOI   ScienceOn
28 Walmsly D, Wiles PG. Early Ioss of neurogenic inflammation in the human diabetic foot. Clinical Science 80:605 610, 1991   DOI
29 Lembeck F, Donnerer J, Bartho L. Inhibition of neurogenic vasodilatation and plasma extravasation by substance P antagonists, somatostatin and [D $Met^2$, $Pro^5$] encephalinamide. Eur J Pharmac 85:171 176, 1982.   DOI   ScienceOn
30 Hokfelt T, Pernow B, Wahren J. Substance P: a pioneer amongst neuropeptides. J Intern Med 249:27 40, 2001   PUBMED
31 Kim S, Fan FC, Chen RYZ, Simchon S, Schuessler GB, Chien S. Effects of changes in the systemic hemodynamic parameters in pulpal hemodynamics. J Endodont 63:394 399, 1980
32 Yonehara N, Sawada T, Matsuura H, Inoki R. Influence of electro acupuncture on the release of sub stance P and the potential evoked by tooth pulp stimulation in the trigeminal nucleus caudalis of the rabbit. Neurosci Lett 142(1):53 56, 1992   DOI   ScienceOn
33 Kim S. Microcirculation of the dental pulp in health and disease. J Endodont 11:465 471, 1985   DOI   PUBMED   ScienceOn
34 Roberts RGD, Westerman RA, Widdop RE, Kotzmann RR, Payne R. Effects of capsaicin on cutaneous vasodilator responses in humans. Agent Act 37:53 59, 1992   DOI
35 Heyeraas K, Kvinnsland I. Tissue pressure and blood flow in pulpal inflammation. Proc Finn Dent Soc 88(1):393-401, 1992
36 Olgart L, Gazelius B. Enhanced vasodilation in sensory denervated tooth pulp by substance P (SP). Reg Pep 22: (Abstract)137, 1988
37 Olgart L, Gazelius B, Brodin E, Nilsson G. Release of substance P like immunoreactivity from the Dental Pulp. Acta Physiol Scand 101:510 512, 1977   DOI   ScienceOn
38 Liu M, Pertl C, Markowitz K, Dorscher Kim JE, Kim S. The effects of capsaicin on pulpal blood flow. Proc Finn Dent Soc 88(1):464 467, 1992
39 Berggreen E, Heyeraas KJ. The role of sensory neu ropeptides and nitric oxide on pulpal blood flow and tissue pressure in the ferret. J Dent Res 78(9):1535 1543, 1999   DOI   ScienceOn
40 Watling KJ, Krause JE. The rising sun shines on substance P and related peptides. Trends Pharmacol Sci 14:81 84, 1993   DOI   ScienceOn
41 Raab WHM. Temperature related changes in pulpal microcirculation. Proc Finn Dent Soc 88(1):469 474, 1992
42 Hakanson R, Leander S, Andersson RGG, Horig J. Substance P antagonists release histamine from peritoneal mast celIs. Acta Physiol Scand 117:319 320, 1983   DOI   ScienceOn
43 Louis SM, Jamieson A, Russell NJW, Dockray GJ. The role of substance P and calcitonin gene related peptide in neurogenic plasma extravasation and vasodilation in the rat. Neurosci 32(3):581 586, 1989   DOI   ScienceOn
44 Kim S, Liu M, Simchon S, Dorscher Kim JE. Effects of selected inflammatory mediators on blood flow and vascular permeability in the dental pulp. Proc Finn Dent Soc 88(1):387 392, 1992
45 Kostouros GD. Iontophoretic delivery of pharmacological agents to the dental pulp, an experimental study in the rat, ppl 39, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden, 1996
46 Heyeraas KJ, Kim S, Raab WHM, 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 47:329 343, 1994   DOI   ScienceOn
47 Vongsavan N, Matthews B. Changes in pulpal bloodflow and in fluid flow through dentine produced by autonomic and sensory nerve stimulation in the cat. Proc Finn Dent Soc 88(1):491 497, 1992
48 Kim S. Regulation of pulpal blood flow. J Dent Res 64(spec. iss.):590 596, 1985   DOI   PUBMED
49 Kim S, Dorscher Kim JE, Liu MT, Trowbridge HO. Biphasic pulp blood flow response to substance P in the dog as measured with a radiolabeled, microsphere injection method. Archs Oral Biol 33:305 309, 1988   DOI   ScienceOn