Article Data

  • Views 503
  • Dowloads 62

Original Research

Open Access

Acute Dental Pain and Salivary Biomarkers for Stress and Inflammation in Patients with Pulpal or Periapical Inflammation

  • Sivakami Rethnam Haug1,*,
  • Mihaela Cuida Marthinussen1,2

1Univ Bergen, Fac Med, Dept Clin Dent, Arstadveien 19, N-5009 Bergen, Norway

2Oral Hlth Ctr Expertise Western Norway, Bergen, Norway

DOI: 10.11607/ofph.2007 Vol.33,Issue 2,June 2019 pp.227-233

Submitted: 29 June 2017 Accepted: 27 June 2018

Published: 30 June 2019

*Corresponding Author(s): Sivakami Rethnam Haug E-mail: sivakami.haug@uib.no

Abstract

Aims: To investigate whether acute dental pain due to pulpal or periapical inflammation is associated with increased expression of cortisol and inflammatory markers and mediators in the saliva, as well as changes in salivary flow rate. Methods: Patients experiencing pain (n = 42) were recruited when seeking emergency dental treatment. A 0 to 10 numeric rating scale (NRS) was used as a measure of the severity of pain, and the number of days with pain sensation was also recorded. Unstimulated saliva was collected for 3 minutes (salivary flow measured in mL/minute) and stored at –80°C. Saliva was analyzed for the biomarkers cortisol, C-reactive protein (CRP), and cytokines interleukin-1β (IL-1β) and interleukin-6. In addition, the participants completed a simple questionnaire about stress-inducing factors such as insomnia, dental anxiety, or home/workplace stress. Patients received a dental examination and diagnosis (eg, symptomatic pulpitis/apical periodontitis or acute apical abscess), which was confirmed during dental treatment. The control group (n = 39) consisted of participants without any pain and no known medical or dental problems. Results: Patients experiencing acute pain due to pulpal or periapical inflammation had a mean NRS score of 7.0 ± 2.59. The mean duration of pain was 6.5 ± 7.9 days. There was no significant difference in pain level between male and female subjects, tooth type affected, or diagnosis. Higher levels of cortisol, IL-1β, and IL-6 and increased salivary flow were detected in patients with pain when compared to controls (P < .05). CRP was higher in patients with acute pain compared to control participants without pain, but this difference was not statistically significant. Stress at home or the workplace was reported by 79% of patients experiencing pain and by 28% of control participants. Conclusion: Acute dental pain due to pulpal or periapical inflammation was associated with an increase in salivary cortisol, IL-1β, and IL-6 levels and in salivary flow rate. Stress arising from home or the workplace may aggravate a symptom- free pulpal or periapical inflammation to an acute phase. Inflammation in the pulp and periapical region can have effects in regions remote from the disease site.

Keywords

cortisol;CRP;dental pulp;endodontic;IL-1β;IL-6;salivary flow rate

Cite and Share

Sivakami Rethnam Haug,Mihaela Cuida Marthinussen. Acute Dental Pain and Salivary Biomarkers for Stress and Inflammation in Patients with Pulpal or Periapical Inflammation. Journal of Oral & Facial Pain and Headache. 2019. 33(2);227-233.

References

1. Byers MR. Dental sensory receptors. Int Rev Neurobiol 1984; 25:39–94.

2. Gibbs JL, Melnyk JL, Basbaum AI. Differential TRPV1 and TRPV2 channel expression in dental pulp. J Dent Res 2011; 90:765–770.

3. Lipton JA, Ship JA, Larach-Robinson D. Estimated prevalence and distribution of reported orofacial pain in the United States. J Am Dent Assoc 1993;124:115–121.

4. Awawdeh L, Lundy FT, Shaw C, Lamey PJ, Linden GJ, Kennedy JG. Quantitative analysis of substance P, neurokinin A and cal- citonin gene-related peptide in pulp tissue from painful and healthy human teeth. Int Endod J 2002;35:30–36.

5. Zehnder M, Delaleu N, Du Y, Bickel M. Cytokine gene expres- sion—Part of host defence in pulpitis. Cytokine 2003;22:84–88.

6. Azuma MM, Samuel RO, Gomes-Filho JE, Dezan-Junior E, Cintra LT. The role of IL-6 on apical periodontitis: A systematic review. Int Endod J 2014;47:615–621.

7. Barkhordar RA, Hussain MZ, Hayashi C. Detection of inter- leukin-1 beta in human periapical lesions. Oral Surg Oral Med Oral Pathol 1992;73:334–336.

8. Haug SR, Heyeraas KJ. Modulation of dental inflammation by the sympathetic nervous system. J Dent Res 2006;85:488–495.

9. Yeager MP, Pioli PA, Guyre PM. Cortisol exerts bi-phasic regulation of inflammation in humans. Dose Response 2011;9: 332–347.

10. Strausbaugh HJ, Dallman MF, Levine JD. Repeated, but not acute, stress suppresses inflammatory plasma extravasation. Proc Natl Acad Sci U S A 1999;96:14629–14634.

11. Strausbaugh HJ, Green PG, Dallman MF, Levine JD. Repeated, non-habituating stress suppresses inflammatory plasma ex- travasation by a novel, sympathoadrenal dependent mecha- nism. Eur J Neurosci 2003;17:805–812.

12. Mattila K, Vesanen M, Valtonen V, et al. Effect of treating peri- odontitis on C-reactive protein levels: A pilot study. BMC Infect Dis 2002;2:30.

13. Paraskevas S, Huizinga JD, Loos BG. A systematic review and meta-analyses on C-reactive protein in relation to periodonti- tis. J Clin Periodontol 2008;35:277–290.

14. Alotaibi N, Cloutier L, Khaldoun E, Bois E, Chirat M, SalvanD. Criteria for admission of odontogenic infections at high rsk of deep neck space infection. Eur Ann Otorhinolaryngol Head Neck Dis 2015;132:261–264.

15. Pepys MB. C-reactive protein fifty years on. Lancet 1981;1:653–657.

16. Ylijoki S, Suuronen R, Jousimies-Somer H, Meurman JH, Lindqvist C. Differences between patients with or without the need for intensive care due to severe odontogenic infections. J Oral Maxillofac Surg 2001;59:867–872.

17. Scannapieco FA, Bush RB, Paju S. Associations between peri- odontal disease and risk for atherosclerosis, cardiovascular dis- ease, and stroke. A systematic review. Ann Periodontol 2003; 8:38–53.

18. Cotti E, Mercuro G. Apical periodontitis and cardiovascular diseases: Previous findings and ongoing research. Int Endod J 2015;48:926–932.

19. Niedzielska I, Chudek J, Kowol I, et al. The odontogenic-related microinflammation in patients with chronic kidney disease. Ren Fail 2014;36:883–888.

20. Hellhammer DH, Wüst S, Kudielka BM. Salivary cortisol as a biomarker in stress research. Psychoneuroendocrinology 2009;34:163–171.

21. Lee YH, Wong DT. Saliva: An emerging biofluid for early detec- tion of diseases. Am J Dent 2009;22:241–248.

22. Miller CS, Foley JD, Bailey AL, et al. Current developments in salivary diagnostics. Biomark Med 2010;4:171–189.

23. Dawes C. Circadian rhythms in human salivary flow rate and composition. J Physiol 1972;220:529–545.

24. Arvidson NG, Gudbjörnsson B, Elfman L, Rydén AC, Tötterman TH, Hällgren R. Circadian rhythm of serum interleukin-6 in rheumatoid arthritis. Ann Rheum Dis 1994;53:521–524.

25. Haug SR, Berggreen E, Heyeraas KJ. The effect of unilat- eral sympathectomy and cavity preparation on peptidergic nerves and immune cells in rat dental pulp. Exp Neurol 2001; 169:182–190.

26. Haug SR, Brudvik P, Fristad I, Heyeraas KJ. Sympathectomy causes increased root resorption after orthodontic tooth move- ment in rats: Immunohistochemical study. Cell Tissue Res 2003;313:167–175.

27. Haug SR, Heyeraas KJ. Effects of sympathectomy on experi- mentally induced pulpal inflammation and periapical lesions in rats. Neuroscience 2003;120:827–836.

28. Mizawa M, Yamaguchi M, Ueda C, Makino T, Shimizu T. Stress evaluation in adult patients with atopic dermatitis using salivary cortisol. Biomed Res Int 2013;2013:138027.

29. Laudat MH, Cerdas S, Fournier C, Guiban D, Guilhaume B, Luton JP. Salivary cortisol measurement: A practical approach to assess pituitary-adrenal function. J Clin Endocrinol Metab 1988;66:343–348.

30. Zumoff B, Fukushima DK, Weitzman ED, Kream J, Hellman L. The sex difference in plasma cortisol concentration in man. J Clin Endocrinol Metab 1974;39:805–808.

31. Naumova EA, Faber S, Lindner P, et al. Parallel study about the effects of psychotherapy on patients with dental phobia deter- mined by anxiety scores and saliva secretion and composition. BMC Oral Health 2016;17:32.

32. van Gulik L, Ahlers S, van Dijk M, et al. Procedural pain does not raise plasma levels of cortisol or catecholamines in adult intensive care patients after cardiac surgery. Anaesth Intensive Care 2016;44:52–56.

33. Kirschbaum C, Wüst S, Hellhammer D. Consistent sex dif- ferences in cortisol responses to psychological stress. Psychosom Med 1992;54:648–657.

34. Vig RS, Forsythe P, Vliagoftis H. The role of stress in asth- ma: Insight from studies on the effect of acute and chronic stressors in models of airway inflammation. Ann N Y Acad Sci 2006;1088:65–77.

35. Koray M, Dülger O, Ak G, et al. The evaluation of anxiety and salivary cortisol levels in patients with oral lichen planus. Oral Dis 2003;9:298–301.

36. Wright RJ, Cohen RT, Cohen S. The impact of stress on the development and expression of atopy. Curr Opin Allergy Clin Immunol 2005;5:23–29.

37. Chen E, Miller GE. Stress and inflammation in exacerbations of asthma. Brain Behav Immun 2007;21:993–999.

38. Katayama I, Bae SJ, Hamasaki Y, et al. Stress response, tachy- kinin, and cutaneous inflammation. J Investig Dermatol Symp Proc 2001;6:81–86.

39. Liezmann C, Klapp B, Peters EM. Stress, atopy and allergy: A re-evaluation from a psychoneuroimmunologic perspective. Dermatoendocrinol 2011;3:37–40.

40. Pavlovic S, Daniltchenko M, Tobin DJ, et al. Further exploring the brain-skin connection: Stress worsens dermatitis via sub- stance P-dependent neurogenic inflammation in mice. J Invest Dermatol 2008;128:434–446.

41. Olgart L, Gazelius B, Brodin E, Nilsson G. Release of sub- stance P-like immunoreactivity from the dental pulp. Acta Physiol Scand 1977;101:510–512.

42. Hasler JE, Mitchell DF. Painless pulpitis. J Am Dent Assoc 1970;81:671–677.

43. Michaelson PL, Holland GR. Is pulpitis painful? Int Endod J 2002;35:829–832.

44. Bender IB. Pulpal pain diagnosis—A review. J Endod 2000; 26:175–179.

45. Mudie AS, Holland GR. Local opioids in the inflamed dental pulp. J Endod 2006;32:319–323.

46. Sessle BJ. Relevance of psychosocial factors in oral and fa- cial pain and headache [editorial]. J Oral Facial Pain Headache 2017;31:197–198.

47. Tamura T, Udagawa N, Takahashi N, et al. Soluble interleukin-6 receptor triggers osteoclast formation by interleukin 6. Proc Natl Acad Sci U S A 1993;90:11924–11928.

48. Yamazaki K, Honda T, Oda T, et al. Effect of periodontal treat- ment on the C-reactive protein and proinflammatory cytokine levels in Japanese periodontitis patients. J Periodontal Res 2005;40:53–58.

49. Randich A, Gebhart GF. Vagal afferent modulation of nocicep- tion. Brain Res Brain Res Rev 1992;17:77-99.

50. Khasar SG, Green PG, Miao FJ, Levine JD. Vagal modulation of nociception is mediated by adrenomedullary epinephrine in the rat. Eur J Neurosci 2003;17:909–915.

51. Green PG, Miao FJ, Strausbaugh H, Heller P, Janig W, Levine JD. Endocrine and vagal controls of sympathetical- ly dependent neurogenic inflammation. Ann N Y Acad Sci 1998;840:282–288.

52. Martinez JR, Martinez AM. Stimulatory and inhibitory effects of substance P on rat submandibular secretion. J Dent Res 1981;60:1031–1038.

53. Bobyock E, Barbieri EJ, Chernick WS. Effects of substance P and substance P antagonists on rat salivary secretion. J Dent Res 1986;65:1427–1431.

54. Ueha T, Nemoto A, Kurihara K. Studies on the salivary secre- tion induced by substance P in perfused submandibular gland of rat. Proc Finn Dent Soc 1989;85:345–353.

55. Robles TF, Sharma R, Park KS, Harrell L, Yamaguchi M, Shetty V. Utility of a salivary biosensor for objective as- sessment of surgery-related stress. J Oral Maxillofac Surg 2012;70:2256–2263.

56. Wang A, Wang CP, Tu M, Wong DT. Oral biofluid biomarker research: Current status and emerging frontiers. Diagnostics (Basel) 2016;6(4). pii: E45.

57. Punyadeera C, Dimeski G, Kostner K, Beyerlein P, Cooper- White J. One-step homogeneous C reactive protein assay for saliva. J Immunol Methods 2011;373:19–25.

58. Malamud D. Saliva as a diagnostic fluid. Dent Clin North Am2011;55:159–178.

Abstracted / indexed in

Science Citation Index (SCI)

Science Citation Index Expanded (SCIE)

BIOSIS Previews

Scopus

Cumulative Index to Nursing and Allied Health Literature (CINAHL)

Submission Turnaround Time

Conferences

Top