Skip to main content
NCBI home page
Elsevier - PMC COVID-19 Collection logoLink to Elsevier - PMC COVID-19 Collection
. 1998 Jan 21;30(1):109–114. doi: 10.1016/S0306-3623(97)00084-0

A new pharyngitis model using capsaicin in rats

Mutsumi Yamabe 1, Tomokazu Hosokawa 2, Teruro Taoka 1, Miwa Misawa 2,∗
PMCID: PMC7131113  PMID: 9457490

Abstract

  • 1.

    1. Application of capsaicin solution onto the rat pharyngeal mucosa caused a well-reproducible increase in vascular permeability in the pharynx.

  • 2.

    2. Capsaicin-induced pharyngeal inflammation was unaffected by a histamine H1 blocker and non-steroidal anti-inflammatory agents, whereas dexamethasone was effective in its inhibition.

  • 3.

    3. FK224, a dual antagonist of tachykinin NK1 and NK2 receptors, and FK888, a selective antagonist of NK1 receptor, significantly inhibited capsaicin-induced plasma exudation in the pharynx.

  • 4.

    4. In capsaicinized animals, the application of capsaicin solution in the pharyngeal mucosa did not induce pharyngitis.

  • 5.

    5. These results suggest that the mechanism of the capsaicin-induced pharyngitis primarily involves tachykinins.

Keywords: Pharyngitis, capsaicin, anti-inflammatory drugs, tachykinin receptor, rat

References

  1. Buchan P., Adcock J.J. Capsaicin-induced bronchoconstriction in the guinea-pig: contribution of vagal cholinergic reflexes, local axon reflexes and their modulation by BW443c81. Br. J. Pharmac. 1992;105:448–452. doi: 10.1111/j.1476-5381.1992.tb14273.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Buck S.H., Burks T.F. The neuropharmacology of capsaicin: review of some recent observations. Pharmac. Rev. 1986;38:179–226. [PubMed] [Google Scholar]
  3. Buritova J., Honore P., Chapman V., Besson J.M. Concurrent reduction of inflammation and spinal Fos-LI neurons by systemic diclofenac in the rat. Neurosci. Lett. 1995;188:175–178. doi: 10.1016/0304-3940(95)11426-w. [DOI] [PubMed] [Google Scholar]
  4. Finney R.S.H., Somers G.F. The anti-inflammatory activity of glycyrrhetinic acid and derivatives. J. Pharm. Pharmacol. 1958;10:613–620. doi: 10.1111/j.2042-7158.1958.tb10349.x. [DOI] [PubMed] [Google Scholar]
  5. Fujii T., Murai M., Morimoto H., Maeda Y., Yamaoka M., Hagiwara D., Miyake H., Ikari N., Matsuo M. Pharmacological profile of a high affinity dipeptide NK1 receptor antagonist, FK888. Br. J. Pharmac. 1992;107:785–789. doi: 10.1111/j.1476-5381.1992.tb14524.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fujii T. Discovery and pharmacological properties of selective neurokinin-receptor antagonists, FK224 and FK888. Folia Pharmacol. Jpn. 1995;106:193–204. doi: 10.1254/fpj.106.193. [DOI] [PubMed] [Google Scholar]
  7. Gabor M., Razga Z. Development and inhibition of mouse ear oedema induced with capsaicin. Agents Actions. 1992;36:83–86. doi: 10.1007/BF01991233. [DOI] [PubMed] [Google Scholar]
  8. Garret C., Carruette A., Fardin V., Moussaoui S., Peyronel J.F., Blanchard J.C., Laduron P.M. Vol. 88. 1991. Pharmacological properties of a potent and selective nonpeptide substance P antagonist; pp. 10208–10212. (Proc. Natl. Acad. Sci. USA). [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Holzer P. Local effector functions of capsaicin-sensitive sensory nerve endings: involvement of tachykinins, calcitonin gene-related peptide and other neuropeptides. Neuroscience. 1988;24:739–768. doi: 10.1016/0306-4522(88)90064-4. [DOI] [PubMed] [Google Scholar]
  10. Holzer P. Capsaicin: cellular targets, mechanisms of action, and selectivity for thin sensory neurons. Pharmac. Rev. 1991;43:143–201. [PubMed] [Google Scholar]
  11. Hong J.-L., Rodger I.W., Lee L.-Y. Cigarette smoke-induced bronchoconstriction; cholinergic mechanisms, tachykinins, and cyclo-oxygenase products. J. Appl. Physiol. 1995;78:2260–2266. doi: 10.1152/jappl.1995.78.6.2260. [DOI] [PubMed] [Google Scholar]
  12. Ingenito E.P., Pliss L.B., Martins M.A., Ingram R.H., Jr. Effects of capsaicin on mechanical, cellular, and mediator responses to antigen in sensitized guinea pigs. Am. Rev. Respir. Dis. 1991;143:572–577. doi: 10.1164/ajrccm/143.3.572. [DOI] [PubMed] [Google Scholar]
  13. Inoue H., Nagata N., Koshihara Y. Profile of capsaicin-induced mouse ear oedema as neurogenic inflammatory model: comparison with arachidonic acid-induced ear oedema. Br. J. Pharmac. 1993;110:1614–1620. doi: 10.1111/j.1476-5381.1993.tb14009.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Inoue H., Nagata N., Koshihara Y. Involvement of substance P as a mediator in capsaicin-induced mouse ear oedema. Inflammation Res. 1995;44:470–474. doi: 10.1007/BF01837912. [DOI] [PubMed] [Google Scholar]
  15. Iso T., Nakajima N., Suda H., Yamauchi H., Uda K. Passive anaphylaxis in rat conjunctiva and topical effects of antiallergic agents. Ophthal. Res. 1980;12:9–15. [Google Scholar]
  16. Kamei J., Iwamoto Y., Suzuki T., Misawa M., Nagase H., Kasuya Y. Involvement of δ1-opioid receptor antagonism in the antitussive effect of δ-opioid receptor antagonists. Eur. J. Pharmac. 1994;251:291–294. doi: 10.1016/0014-2999(94)90411-1. [DOI] [PubMed] [Google Scholar]
  17. Kenins P. Responses of single nerve fibers to capsaicin applied to the skin. Neurosci. Lett. 1982;29:83–88. doi: 10.1016/0304-3940(82)90369-x. [DOI] [PubMed] [Google Scholar]
  18. Kerezoudis N.P., Olgart L., Edwall L. Evans blue extravasation in rat dental pulp and oral tissues induced by electrical stimulation of the inferior alveolar nerve. Arch. Oral. Biol. 1993;38:893–901. doi: 10.1016/0003-9969(93)90099-8. [DOI] [PubMed] [Google Scholar]
  19. Kuroiwa C., Umeno E., Nogami H., Kano S., Hirose T., Nishima S. Role of tachykinins in bronchoconstriction induced by intravenous administration of bradykinin in guinea-pigs. Eur. Respir. J. 1996;9:741–746. doi: 10.1183/09031936.96.09040741. [DOI] [PubMed] [Google Scholar]
  20. Lang S.D.R., Singh K. The sore throat: when to investigate and when to prescribe. Drugs. 1990;40:854–862. doi: 10.2165/00003495-199040060-00007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lei Y.-H., Barnes P.J., Rogers D.F. Inhibition of neurogenic plasma exudation in guinea pig airways by CP-96,345, a new non-peptide NK1 receptor antagonist. Br. J. Pharmac. 1992;105:261–262. doi: 10.1111/j.1476-5381.1992.tb14243.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lembeck F., Donnerer J., Tsuchiya M., Nagahisa A. The non-peptide tachykinin antagonist, CP-96,345, is a potent inhibitor of neurogenic inflammation. Br. J. Pharmac. 1992;105:527–530. doi: 10.1111/j.1476-5381.1992.tb09013.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lundberg J.M., Saria A. Capsaicin-sensitive vagal neurons involved in control of vascular permeability in rat. Acta Physiol. Scand. 1982;115:521–523. doi: 10.1111/j.1748-1716.1982.tb07116.x. [DOI] [PubMed] [Google Scholar]
  24. Lundberg J.M., Saria A. Capsaicin-induced desensitization of airway mucosa to cigarette smoke, mechanical irritants. Nature (Lond.) 1983;302:251–253. doi: 10.1038/302251a0. [DOI] [PubMed] [Google Scholar]
  25. Lynn B., Ye W., Cotsell B. The actions of capsaicin applied topically to the skin of the rat on C-fiber afferents, antidromic vasodilation and substance P levels. Br. J. Pharmac. 1992;107:400–406. doi: 10.1111/j.1476-5381.1992.tb12758.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Maggi C.A., Meli A. The sensory-efferent function of capsaicin-sensitive sensory neurons. Gen. Pharmac. 1988;19:1–43. doi: 10.1016/0306-3623(88)90002-x. [DOI] [PubMed] [Google Scholar]
  27. Martling C.R. Sensory nerves containing tachykinins and CGRP in the lower airways. Acta Physiol. Scand. 1987;563:1–57. (suppl.) [PubMed] [Google Scholar]
  28. Morimoto H., Murai M., Maeda Y., Yamaoka M., Nishikawa M., Kiyotoh S., Fujii T. FK224, a novel cyclopeptide substance P antagonist with NK1 and NK2 receptor selectivity. J. Pharmac. Exp. Ther. 1992;262:398–402. [PubMed] [Google Scholar]
  29. Murai M., Morimoto H., Maeda Y., Kiyotoh S., Nishikawa M., Fujii T. Effects of FK224, a novel compound NK1 and NK2 receptor antagonist, on airway constriction and airway edema induced by neurokinins and sensory nerve stimulation in guinea pigs. J. Pharmac. Exp. Ther. 1992;262:403–408. [PubMed] [Google Scholar]
  30. Peter G. Streptococcal pharyngitis: current therapy and criteria for evaluation of new agents. Clin. Infect. Dis. 1992;14:S218–S223. doi: 10.1093/clinids/14.supplement_2.s218. (suppl.) [DOI] [PubMed] [Google Scholar]
  31. Roberts A.M., Schultz H.D., Green J.F., Armstrong D.J., Kaufman M.P., Coleridge H.M., Coleridge J.C.G. Reflex tracheal contraction evoked in dogs by bronchodilator prostaglandins E2 and I2. J. Appl. Physiol. 1985;58:1823–1831. doi: 10.1152/jappl.1985.58.6.1823. [DOI] [PubMed] [Google Scholar]
  32. Rogers D.F., Belvisi M.G., Aursudkig B., Evans T.W., Barnes P. Effects and interactions of sensory neuropeptides on airway microvascular leakage in guinea-pigs. Br. J. Pharmac. 1988;95:1109–1116. doi: 10.1111/j.1476-5381.1988.tb11745.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Saria A., Lundberg J.M., Skofitsch G., Lembeck F. Vascular protein leakage in various tissues induced by substance P, capsaicin, bradykinin, serotonin, histamine and by antigen challenge. Naunyn-Schmiedeberg's Arch. Pharmac. 1983;324:212–218. doi: 10.1007/BF00503897. [DOI] [PubMed] [Google Scholar]
  34. Saria A., Martling C.R., Yan Z., Theodorsson-Norheim E., Gamse R., Lundberg J.M. Release of multiple tachykinins from capsaicin-sensitive sensory nerves in the lung by bradykinin, histamine, dimethylphenyl piperazinium, and vagal nerve stimulation. Am. Rev. Respir. Dis. 1988;137:1330–1335. doi: 10.1164/ajrccm/137.6.1330. [DOI] [PubMed] [Google Scholar]
  35. Sheppard L.M., Werkhaven J., Mickelson S., Crissman J.D., Peterson E., Jacobsen G. Effect of steroids or tissue precooling on edema and tissue thermal coagulation after CO2 laser impact. Lasers Surg. Med. 1992;8:108–118. doi: 10.1002/lsm.1900120205. [DOI] [PubMed] [Google Scholar]
  36. Szallasi A., Blumberg P.M. Mechanisms and therapeutic potential of vanilloids (capsaicin-like molecules) Adv. Pharmac. 1993;24:123–155. doi: 10.1016/s1054-3589(08)60936-9. [DOI] [PubMed] [Google Scholar]
  37. Tani E., Senba E., Kokumai S., Masuyama K., Ishikawa T., Tohyama M. Histamine application to the nasal mucosa induces release of calcitonin gene-related peptide and substance P from peripheral terminals of trigeminal ganglion: a morphological study in the guinea pig. Neurosci. Lett. 1990;112:1–6. doi: 10.1016/0304-3940(90)90312-w. [DOI] [PubMed] [Google Scholar]
  38. Vukmir R.B. Adult and pediatric pharyngitis: a review. J. Emerg. Med. 1992;10:607–616. doi: 10.1016/0736-4679(92)90146-K. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Wang J.P., Raung S.L., Lin C.N., Teng C.M. Inhibitory effect of norathyriol, a xanthone from Tripterospermum lanceolatum, on cutaneous plasma extravasation. Eur. J. Pharmac. 1994;251:35–42. doi: 10.1016/0014-2999(94)90440-5. [DOI] [PubMed] [Google Scholar]
  40. Yamatake Y., Sasagawa S., Yanaura S., Kobayashi N. Involvement of histamine H1- and H2-receptors in induced asthmas in dogs. Jpn. J. Pharmac. 1977;27:791–797. doi: 10.1254/jjp.27.791. [DOI] [PubMed] [Google Scholar]
  41. Yonei Y., Holzer P., Guth P.H. Laparotomy-induced gastric protection against ethanol injury is mediated by capsaicin-sensitive sensory neurons. Gastroenterology. 1990;99:3–9. doi: 10.1016/0016-5085(90)91222-r. [DOI] [PubMed] [Google Scholar]
  42. Yoshihara S., Chan B., Yamawaki I., Geppetti P., Ricciardolo F.L.M., Massion P.P., Nadel J.A. Plasma extravasation in the rat trachea induced by cold air is mediated by tachykinin release from sensory nerves. Am. J. Respir. Crit. Care Med. 1995;151:1011–1017. doi: 10.1164/ajrccm/151.4.1011. [DOI] [PubMed] [Google Scholar]
  43. Yoshihara S., Geppetti P., Hara M., Linden A., Ricciardolo F.L.M., Chan B., Nadel J.A. Cold air-induced bronchoconstriction is mediated by tachykinin and kinin release in guinea pigs. Eur. J. Pharmac. 1996;296:291–296. doi: 10.1016/0014-2999(95)00719-9. [DOI] [PubMed] [Google Scholar]

Articles from General Pharmacology are provided here courtesy of Elsevier

RESOURCES