Skip to main content

Advertisement

Log in

Opiorphin levels in fluids of burning mouth syndrome patients: a case-control study

  • Original Article
  • Published:
Clinical Oral Investigations Aims and scope Submit manuscript

Abstract

Objectives

Idiopathic Burning mouth syndrome (iBMS) is a poorly understood affection characterized by persistent pain in the oral cavity without any clinical or biological abnormality. Opiorphin is a natural inhibitor of enkephalin-inactivating ectopeptidases, mainly produced by salivary glands, that has demonstrated analgesic properties. The objective of the present case-control study was to test the hypothesis of a decrease in opiorphin levels in iBMS patients.

Materials and methods

Twenty-one iBMS patients and 21 matched controls subjects were included between 2011 and 2013. Submandibular and sublingual salivary, blood, and urinary opiorphin levels of iBMS patients were compared to controls.

Results

Results are expressed as mean values ± SD and compared using the Wilcoxon Signed Rank test. Correlations were analyzed with Spearman coefficient. The level of significance was fixed at p < 0.05. Opiorphin levels in iBMS and controls were respectively (in ng/ml) in basal saliva: 37.8 ± 42.5 and 67.6 ± 188.9 (p = NS); stimulated saliva: 28.8 ± 25.3 and 31.1 ± 29.1 (p = NS); blood: 4.6 ± 5.4 and 1.9 ± 1.4 (p < 0.05); and urines: 68.5 ± 259.8 and 8.9 ± 6.2 (p = NS).

Clinical relevance

In conclusion, the lack of significative difference in salivary opiorphin levels between iBMS and controls does not favor a direct local role for opiorphin in the etiopathogeny of iBMS. However, higher blood opiorphin levels may reflect a systemic dysregulation in iBMS.

Trial registration

NCT02686359 https://clinicaltrials.gov/ct2/show/NCT02686359

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

Similar content being viewed by others

References

  1. Merskey H (2007) The taxonomy of pain. Med Clin North Am 91(13–20):vii

    Google Scholar 

  2. Kohorst JJ, Bruce AJ, Torgerson RR, Schenck LA, Davis MD (2015) The prevalence of burning mouth syndrome: a population-based study. Br J Dermatol 172:1654–1656

    Article  PubMed  PubMed Central  Google Scholar 

  3. Grushka M (1987) Clinical features of burning mouth syndrome. Oral Surg Oral Med Oral Pathol 63:30–36

    Article  PubMed  Google Scholar 

  4. Scala A, Checchi L, Montevecchi M et al (2003) Update on burning mouth syndrome: overview and patient management. Crit Rev Oral Biol Med 14:275–291

    Article  PubMed  Google Scholar 

  5. Forssell H, Jääskeläinen S, List T et al (2014) An update on pathophysiological mechanisms related to idiopathic oro-facial pain conditions with implications for management. J Oral Rehabil 42:300–322

    Article  PubMed  Google Scholar 

  6. Jääskeläinen SK (2012) Pathophysiology of primary burning mouth syndrome. Clin Neurophysiol Off J Int Fed Clin Neurophysiol 123:71–77

    Article  Google Scholar 

  7. Kolkka-Palomaa M, Jääskeläinen SK, Laine MA et al (2015) Pathophysiology of primary burning mouth syndrome with special focus on taste dysfunction: a review. Oral Dis 21:937–948

    Article  PubMed  Google Scholar 

  8. Buchanan JA, Zakrzewska JM. (2016) Burning mouth syndrome. BMJ Clin. Evid. 7:1301.

  9. Rougeot C, Messaoudi M, Hermitte V et al (2003) Sialorphin, a natural inhibitor of rat membrane-bound neutral endopeptidase that displays analgesic activity. Proc Natl Acad Sci U S A 100:8549–8554

    Article  PubMed  PubMed Central  Google Scholar 

  10. Wisner A, Dufour E, Messaoudi M et al (2006) Human opiorphin, a natural antinociceptive modulator of opioid-dependent pathways. Proc Natl Acad Sci 103:17979–17984

    Article  PubMed  PubMed Central  Google Scholar 

  11. bgee.uni.ch; http://bgee.unil.ch/bgee/bgee?page=gene&action=expression&gene_id=ENSG00000171199).

  12. Tóth F, Tóth G, Benyhe S et al (2012) Opiorphin highly improves the specific binding and affinity of MERF and MEGY to rat brain opioid receptors. Regul Pept 178:71–75

    Article  PubMed  Google Scholar 

  13. König M, Zimmer AM, Steiner H et al (1996) Pain responses, anxiety and aggression in mice deficient in pre-proenkephalin. Nature 383:535–538

    Article  PubMed  Google Scholar 

  14. Filliol D, Ghozland S, Chluba J et al (2000) Mice deficient for delta- and mu-opioid receptors exhibit opposing alterations of emotional responses. Nat Genet 25:195–200

    Article  PubMed  Google Scholar 

  15. Tian X, Chen J, Xiong W et al (2009) Effects and underlying mechanisms of human opiorphin on colonic motility and nociception in mice. Peptides 30:1348–1354

    Article  PubMed  Google Scholar 

  16. Javelot H, Messaoudi M, Garnier S et al (2010) Human opiorphin is a naturally occurring antidepressant acting selectively on enkephalin-dependent delta-opioid pathways. J Physiol Pharmacol 61:355–362

    PubMed  Google Scholar 

  17. Marini M, Roda LG (2000) Enkephalin-degrading enzymes and their inhibitors in human saliva. Peptides 21:125–135

    Article  PubMed  Google Scholar 

  18. Tepperman FS, Jarvis A, Hirst M (1988) Detection of enkephalin-like immunoreactive material in human saliva. Prog Neuro-Psychopharmacol Biol Psychiatry 12:285–289

    Article  Google Scholar 

  19. Pikula DL, Harris EF, Desiderio DM et al (1992) Methionine enkephalin-like, substance P-like, and beta-endorphin-like immunoreactivity in human parotid saliva. Arch Oral Biol 37:705–709

    Article  PubMed  Google Scholar 

  20. Takeyama M, Mori K, Takayama F et al (1990) Enzyme immunoassay of a substance P-like immunoreactive substance in human plasma and saliva. Chem Pharm Bull (Tokyo) 38:3494–3496

    Article  Google Scholar 

  21. Rougeot C, Robert F, Menz L et al (2010) Systemically active human opiorphin is a potent yet non-addictive analgesic without drug tolerance effects. J Physiol Pharmacol 61:483–490

    PubMed  Google Scholar 

  22. Dufour E, Villard-Saussine S, Mellon V, Leandri R, Jouannet P, Ungeheuer MN and Rougeot C. (2013) Opiorphin Secretion Pattern in Healthy Volunteers: Gender Difference and Organ Specificity. Biochem. Anal. Biochem. ; available at http://www.omicsonline.org/biochemistry-and-analytical-biochemistry- abstract.php?abstract_id = 15749 (accessed 10 october 2015).

  23. Bergdahl J, Anneroth G (1993) Burning mouth syndrome: literature review and model for research and management. J. Oral Pathol. Med. 22:433–438

    Article  PubMed  Google Scholar 

  24. Braud A, Touré B, Agbo-Godeau S et al (2013) Characteristics of pain assessed with visual analog scale and questionnaire in burning mouth syndrome patients: a pilot study. J Orofac Pain 27:235–242

    PubMed  Google Scholar 

  25. Zigmond AS, Snaith RP (1983) The hospital anxiety and depression scale. Acta Psychiatr Scand 67:361–370

    Article  PubMed  Google Scholar 

  26. Hershkovich O, Nagler RM (2004) Biochemical analysis of saliva and taste acuity evaluation in patients with burning mouth syndrome, xerostomia and/or gustatory disturbances. Arch Oral Biol 49:515–522

    Article  PubMed  Google Scholar 

  27. de Moura SAB, de Sousa JMA, Lima DF et al (2007) Burning mouth syndrome (BMS): sialometric and sialochemical analysis and salivary protein profile. Gerodontology 24:173–176

    Article  PubMed  Google Scholar 

  28. Borelli V, Marchioli A, Di Taranto R et al (2010) Neuropeptides in saliva of subjects with burning mouth syndrome: a pilot study. Oral Dis 16:365–374

    Article  PubMed  Google Scholar 

  29. Spadari F, Venesia P, Azzi L et al (2015) Low basal salivary flow and burning mouth syndrome: new evidence in this enigmatic pathology. J Oral Pathol Med 44:229–233

    Article  PubMed  Google Scholar 

  30. Imura H, Shimada M, Yamazaki Y et al (2015) Characteristic changes of saliva and taste in burning mouth syndrome patients. J Oral Pathol Med doi. doi:10.1111/jop.12350

    Google Scholar 

  31. Granot M, Nagler RM (2005) Association between regional idiopathic neuropathy and salivary involvement as the possible mechanism for oral sensory complaints. J Pain Off J Am Pain Soc 6:581–587

    Article  Google Scholar 

  32. Rougeot C, Rosinski-Chupin I, Njamkepo E et al (1994) Selective processing of submandibular rat 1 protein at dibasic cleavage sites. Salivary and bloodstream secretion products Eur J Biochem FEBS 219:765–773

    Article  Google Scholar 

  33. Rougeot C, Vienet R, Cardona A et al (1997) Targets for SMR1-pentapeptide suggest a link between the circulating peptide and mineral transport. Am J Phys 273:R1309–R1320

    Google Scholar 

  34. Lamey P-J, Freeman R, Eddie S-A et al (2005) Vulnerability and presenting symptoms in burning mouth syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 99:48–54

    Article  PubMed  Google Scholar 

  35. de Souza FTA, Teixeira AL, Amaral TMP et al (2012) Psychiatric disorders in burning mouth syndrome. J Psychosom Res 72:142–146

    Article  PubMed  Google Scholar 

  36. Adamo D, Schiavone V, Aria M et al (2013) Sleep disturbance in patients with burning mouth syndrome: a case-control study. J Orofac Pain 27:304–313

    Article  PubMed  Google Scholar 

  37. Lopez-Jornet P, Lucero-Berdugo M, Castillo-Felipe C et al (2015) Assessment of self-reported sleep disturbance and psychological status in patients with burning mouth syndrome. J Eur Acad Dermatol Venereol 29:1285–1290

    Article  PubMed  Google Scholar 

  38. Asmundson GJG, Katz J (2009) Understanding the co-occurrence of anxiety disorders and chronic pain: state-of-the-art. Depress Anxiety 26:888–901

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by a grant from Assistance Publique-Hôpitaux de Paris (PHRC OPIODYN# P081106) and Institut Pasteur.

We wish to thank Dr. Nathan Moreau for his help in English editing and the team of the URC: A Mallet, A Bissery, and L Gambotti, for their invaluable conceptual and logistical support; N Cozic for the statistical analysis, and the clinical research assistants V Mellon, V Bessirard, and L Revazian, for their help in Institut Pasteur and GHPS.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yves Boucher.

Ethics declarations

The study followed the ethical principles of the Helsinki declaration and Good Clinical Practice. All subjects provided written informed consent before inclusion and had their anonymity respected throughout the course of the study. The study was registered under # NCT02686359 (https://clinicaltrials.gov). The reporting of data followed the STROBE statement.

Conflict of interest

The authors declare that they have no conflict of interest.

Funding

The work was supported by Assistance Publique-Hôpitaux de Paris (#P081106) and conducted at the Groupe Hospitalier Pitié Salpetrière (GHPS) and Institut Pasteur, France.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study. All subjects provided written informed consent before inclusion and had their anonymity respected throughout the course of the study. The study was registered under #NCT02686359 (https://clinicaltrials.gov).

Electronic supplementary material

ESM 1

(DOC 27 kb)

ESM 2

(DOC 27 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Boucher, Y., Braud, A., Dufour, E. et al. Opiorphin levels in fluids of burning mouth syndrome patients: a case-control study. Clin Oral Invest 21, 2157–2164 (2017). https://doi.org/10.1007/s00784-016-1991-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00784-016-1991-0

Keywords

Navigation