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
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References
Merskey H (2007) The taxonomy of pain. Med Clin North Am 91(13–20):vii
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
Grushka M (1987) Clinical features of burning mouth syndrome. Oral Surg Oral Med Oral Pathol 63:30–36
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
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
Jääskeläinen SK (2012) Pathophysiology of primary burning mouth syndrome. Clin Neurophysiol Off J Int Fed Clin Neurophysiol 123:71–77
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
Buchanan JA, Zakrzewska JM. (2016) Burning mouth syndrome. BMJ Clin. Evid. 7:1301.
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
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
bgee.uni.ch; http://bgee.unil.ch/bgee/bgee?page=gene&action=expression&gene_id=ENSG00000171199).
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
König M, Zimmer AM, Steiner H et al (1996) Pain responses, anxiety and aggression in mice deficient in pre-proenkephalin. Nature 383:535–538
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
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
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
Marini M, Roda LG (2000) Enkephalin-degrading enzymes and their inhibitors in human saliva. Peptides 21:125–135
Tepperman FS, Jarvis A, Hirst M (1988) Detection of enkephalin-like immunoreactive material in human saliva. Prog Neuro-Psychopharmacol Biol Psychiatry 12:285–289
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
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
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
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).
Bergdahl J, Anneroth G (1993) Burning mouth syndrome: literature review and model for research and management. J. Oral Pathol. Med. 22:433–438
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
Zigmond AS, Snaith RP (1983) The hospital anxiety and depression scale. Acta Psychiatr Scand 67:361–370
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
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
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
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
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
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
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
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
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
de Souza FTA, Teixeira AL, Amaral TMP et al (2012) Psychiatric disorders in burning mouth syndrome. J Psychosom Res 72:142–146
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
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
Asmundson GJG, Katz J (2009) Understanding the co-occurrence of anxiety disorders and chronic pain: state-of-the-art. Depress Anxiety 26:888–901
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.
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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.
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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).
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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
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DOI: https://doi.org/10.1007/s00784-016-1991-0