Skip to main content

Advertisement

Log in

Tissue-selective inflammation in the oral cavity of the rat

  • Original Article
  • Published:
Inflammopharmacology Aims and scope Submit manuscript

Abstract

In the current study, carrageenan (CG; 100–1000 μg/site) was injected intraorally in the cheeks of Holtzman or Wistar rats to evaluate the consequences of administration of a non-immunogenic stimulus in the orofacial region. Subsequent inflammation was measured as oedema (increased thickness of the cheek wall using digital calipers), relative to the other cheek injected with saline. Oedema formation and tissue collection for histopathological studies were assessed at 0.5, 1, 2, 3, 4, 6, 24, 48, 72, 96, 120 and 144 h after injection. In parallel, other groups of rats were injected with CG in the hind paw, to provide a reference response. The inhibitor of prostaglandin biosynthesis, indomethacin, and antagonists of histamine, serotonin and NK1 receptors were injected s.c., 0.5 h before CG. CG induced a dose-related oedema more rapidly from 0 to 2 h which lasted for at least 72 h, showing a biphasic profile (peak at 2 and 24 h), compared with the monophasic oedema induced in rat paws (maximal duration of 24 h). Histopathological analysis of the CG-injected cheek revealed oedema formation with little leukocyte recruitment at 1–3 h, mast cell degranulation at 6 h, and a mixed polymorphonuclear and mononuclear cell infiltrate by 24 h. Histamine and serotonin antagonists and indomethacin, but not the NK1 antagonist, decreased cheek oedema in the first 4 h following carrageenan. Taken together, our data indicated important differences in the pattern of inflammation between the oral cavity and the paw which will determine the therapeutic approach to the treatment of inflammatory conditions in the oral cavity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Aleksandrov PN, Speranskaya TV (1988) Dynamics of carrageenan inflammation with the application of lithium hydroxybutyrate. Byulleten ‘Eksperimental’ noi Biologii I Meditsiny 106:233–235

    CAS  Google Scholar 

  • Aleksandrov PN, Speranskaya TV, Bobkov YG, Zagorevskii VA, Zikov DA (1986) Dynamics of carrageenan-induced inflammation under conditions of experimental therapy. Byulleten ‘Eksperimental’ noi Biologii I Meditsiny 101:149–151

    CAS  Google Scholar 

  • Baumgart DC, Carding SR (2007) Inflammatory bowel disease: cause and immunobiology. Lancet 369:1627–1640

    Article  CAS  PubMed  Google Scholar 

  • Birch Pj, Harrison SM, Hayes AG, Rogers H, Tyers MB (1992) The non-peptide NK1 receptor antagonist (±)-CP-96,345 produces antinociceptive and anti-oedema effects in the rat. Brit J Pharmacol 105:508–510

    Article  CAS  Google Scholar 

  • Bonica JJ (1990) General considerations of the pain in the head. In: Bonica JJ (eds with collaboration) The management of pain, 2nd edn. Lea and Febinger, Philadelphia, pp 651–675

  • Chang Y, Chen TL, Sheu JR, Chen RM (2005) Suppressive effects of ketamine on macrophage functions. Toxicol Appl Pharmacol 204:27–35

    Article  CAS  PubMed  Google Scholar 

  • Chen TL, Chang CC, Lin YL, Ueng YF, Chen RM (2009) Signal-transducing mechanisms of ketamine-caused inhibition of interleukin-1 beta gene expression in lipopolysaccharide-stimulated murine macrophage-like Raw 264.7 cells. Toxicol Appl Pharmacol 240:15–25

    Article  CAS  PubMed  Google Scholar 

  • Christopoulos A, Moubayed SP, Nader M-E, Ayad T, Ghannoum JE, Meyers AD (2015) Mouth anatomy. In: Drugs, diseases and procedures, Medscape reference available at http://emedicine.medscape.com/article/1899122-overview. Accessed 11 Nov 2015

  • Clarke M, Razmjou S, Prowse N, Dwyer Z, Litteljohn D, Pentz R, Anisman H, Hayley S (2016) Ketamine modulates hippocampal neurogenesis and pro-inflammatory cytokines but not stressor induced neurochemical changes. Neuropharmacology. doi:10.1016/j.neuropharm.2016.04.021 [Epub ahead of print]

    Google Scholar 

  • Denadai-Souza A, Camargo LDL, Ribela MTCP, Keeble JE, Muscará MN (2009) Participation of peripheral tachykinin NK1 receptors in the carrageenan-induced inflammation of the rat temporomandibular joint. Eur J Pain 13:812–819

    Article  CAS  PubMed  Google Scholar 

  • Di Rosa M (1972) Biological properties of carrageenan. J Pharm Pharmacol 24:89–102

    Article  PubMed  Google Scholar 

  • Eady RAJ (1979) The mast cell in diseases of the skin. In: Pepys J, Edwards AM (eds) Proceedings of an international symposium. Part IV—skin diseases, pp 544–549

  • Frade TIC, Rego IMG, Silva JO, Cassali GD, Bakhle YS, Francischi JN (2013) Comparative inflammation: longer duration of inflammation in the oral cavity than in rat paws. In: XII world congress of inflammation, Natal, RN, Brazil, pp 61

  • Francischi JN, Dias MF, Rocha OA, Castro MSA, Tatsuo MAKF, Farinelli P, Pacheco CMF, Ferreira-Alves DL, Sirois P (1996) Pharmacological characterization of sephadex-induced oedema in rat paws: predominant role of serotonin and platelet activating factor. Int Arch Allergy Immunol 109:398–406

    Article  CAS  PubMed  Google Scholar 

  • Garlet GP, Cardoso CR, Silva TA, Ferreira BR, Ávila-Campos MJ, Cunha FQ, Silva JS (2006) Cytokine pattern determines the progression of experimental periodontal disease induced by Actinobacillus actinomycetemcomitans through the modulation of MMMPs, RANKL, and their physiological inhibitors. Oral Microbiol Immunol 21:12–20

    Article  CAS  PubMed  Google Scholar 

  • Gyorfi A, Fazekas A, Posch E, Irmes F, Rosivall L (1991) Role of histamine in the development of neurogenic inflammation of rat oral mucosa. Agents Actions 32:229–236

    Article  CAS  PubMed  Google Scholar 

  • Gyorfi A, Fazekas A, Rosivall L (1992) Neurogenic inflammation and the oral mucosa. J Clin Periodontol 19:731–736

    Article  CAS  PubMed  Google Scholar 

  • Hokfelt T, Pernow B, Wahren J (2001) History of a pioneering neuropeptide: substance P. J Intern Med 249:27–40

    Article  CAS  PubMed  Google Scholar 

  • Jancsó N, Jancsó-Gabor A, Szolcsányi J (1968) The role of sensory nerve endings in neurogenic inflammation induced in human skin and in the eye and paw of the rat. Brit J Pharmacol Chemother 33:32–41

    Article  Google Scholar 

  • Klausen B (1991) Microbiological and immunological aspects of experimental periodontal disease in rats: a review article. J Periodontol 62:59–73

    Article  CAS  PubMed  Google Scholar 

  • Mak K, Manji A, Gallant-Behm C, Wiebe C, Hart DA, Larjava H, Hakkinen L (2009) Scarless healing of oral mucosa is characterized by faster resolution of inflammation and control of myofibroblast action compared to skin wounds in the red Duroc pig model. J Dermatol Sci 56:168–180

    Article  CAS  PubMed  Google Scholar 

  • Maltos KLM, Menezes GB, Caliari MV, Rocha OA, Santos JMM, Alves DLF, Duarte IDG, Francischi JN (2004) Vascular and cellular responses to pro-inflammatory stimuli in rat dental pulp. Arch Oral Biol 49:443–450

    Article  CAS  PubMed  Google Scholar 

  • Marenholz I, Heizmann CW, Fritz G (2004) S100 proteins in mouse and man: from evolution to function and pathology (including an update of the nomenclature). Biochem Biophys Res Commun 322:1111–1122

    Article  CAS  PubMed  Google Scholar 

  • Mukherjee A, Hale VG, Borga O, Stein R (1996) Predictability of the clinical potency of NSAIDs from the preclinical pharmacodynamics in rats. Inflamm Res 45:531–540

    Article  CAS  PubMed  Google Scholar 

  • Pacheco CMF, Tavares CAP, Coelho PMZ, Rocha OA, Santos JMM, Prado FRM, Francischi JN (1997) Pharmacological evidence supporting a role for IL-1, IL-2 and serotonin in the inflammation induced by Schistosoma mansoni soluble egg antigen (SEA) in rat paws. Mediators Inflamm 7:261–267

    Article  Google Scholar 

  • Pacheco CMF, JrC Queiroz, Maltos KLM, Caliari MV, Rocha OA, Francischi JN (2007) Local opioids in a model of periodontal disease in rats. Arch Oral Biol 52:677–683

    Article  CAS  PubMed  Google Scholar 

  • Paiva-Lima P, Bakhle YS, Francischi JN (2014) Dual effects of RHO-kinase inhibitors on a rat model of inflammatory pain. Pain Res Manag 19:e-172–e-178

    Article  Google Scholar 

  • Parrat JR, West GB (1957) 5-Hydroxytryptamine and tissue mast cells. J Physiol (London) 137:169–178

    Article  Google Scholar 

  • Puri N, Roche PA (2008) Mast cells possess distinct secretory granule subsets whose exocytosis is regulated by different SNARE isoforms. PNAS 105:2580–2585

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Queiroz-Jr CM, Pacheco CMF, Maltos KLM, Caliari MV, Duarte IDG, Francischi JN (2009) Role of systemic and local administration of selective inhibitors of cyclooxygenase 1 and 2 in an experimental model of periodontal disease in rats. J Period Res 44:153–160

    Article  Google Scholar 

  • Richardson JD, Vasko MR (2002) Cellular mechanisms of neurogenic inflammation. J Pharmacol Exp Ther 302:839–845

    Article  CAS  PubMed  Google Scholar 

  • Rowley DA, Benditt EP (1956) 5- Hydroxytryptamine and histamine as mediators of the vascular injury produced by agents which damage mast cells in rats. J Exp Med 103:399–412

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Szpaderska AM, Walsh CG, Steinberg MJ, DiPietro LA (2005) Distinct patterns of angiogenesis in oral and skin wounds. J Dent Res 84:309–314

    Article  CAS  PubMed  Google Scholar 

  • Vane JR, Bakhle YS, Botting RM (1998) Cyclooxygenases 1 and 2. Annu Rev Pharmacol Toxicol 38:97–120

    Article  CAS  PubMed  Google Scholar 

  • Vinegar R, Truax JF, Selph JL, Johnston PR, Venable AL, McKenzie KK (1987) Pathway to carrageenan-induced inflammation in the hind limb of the rat. Fed Proc 46:118–126

    CAS  PubMed  Google Scholar 

  • Ward JL, Harting MT, Cox CS Jr, Mercer DW (2011) Effects of ketamine on endotoxin and traumatic brain injury induced cytokine production in the rat. J Trauma 70:1471–1479

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wasserman SI (1979) The mast cell and the inflammatory response. In: Pepys J, Edwards AM (eds) Proceedings of an international symposium, Part 1, pp 9–20

  • Wernersson S, Pejler G (2014) Mast cell secretory granules: armed for battle. Nat Rev Immunol 14:478–494

    Article  CAS  PubMed  Google Scholar 

  • Winter CA, Risley EA, Nuss GW (1962) Carrageenin-induced oedema in hind paw of the rat as an assay for antiinflammatory drugs. Proc Soc Exp Biol Med 111:544–547

    Article  CAS  PubMed  Google Scholar 

  • Xavier RJ, Podolski DK (2007) Unravelling the pathogenesis of inflammatory bowel disease. Nature 448:427–434

    Article  CAS  PubMed  Google Scholar 

  • Yavuz G, Akbay C (1989) Comparison of carrageenan-induced experimental inflammation in cheek and on dorsum of guinea-pigs. J Dental Fac Ankara Univ 16:433–438

    CAS  Google Scholar 

Download references

Acknowledgments

The authors wish to thank the Brazilian agencies Conselho Nacional de Pesquisa (CNPq) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) for their financial support.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Janetti Nogueira de Francischi.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Frade, T.I.C., dos Reis, D.C., Cassali, G.D. et al. Tissue-selective inflammation in the oral cavity of the rat. Inflammopharmacol 24, 145–153 (2016). https://doi.org/10.1007/s10787-016-0269-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10787-016-0269-0

Keywords

Navigation