Abstract
Objectives
Opiorphin is a pentapeptide isolated from human saliva that suppresses pain from chemically induced inflammation and acute physical pain. Burning mouth syndrome (BMS) is a chronic condition of a burning sensation in the mouth, where no underlying dental or medical cause can be identified. We aimed to measure the level of opiorphin in whole unstimulated (UWS) and stimulated (SWS) saliva of patients with BMS.
Materials and methods
Originally developed and validated LC-MS/MS method was used for opiorphin quantification. Samples were obtained from 29 BMS patients and 29 age- and sex-matched controls.
Results
The average concentration of opiorphin in UWS and SWS in the BMS group was 8.13 ± 6.45 and 5.82 ± 3.59 ng/ml, respectively. Opiorphin in BMS patients’ UWS was significantly higher, compared to the control group (t = 2.5898; p = 0.0122). SWS opiorphin levels were higher, but not significantly, in BMS patients than in controls.
Conclusions
Our results indicate that higher quantities of salivary opiorphin in BMS may be a consequence of chronic pain, but we cannot exclude that they occur as a result of emotional and behavioral imbalances possibly associated with BMS. To our knowledge, this is the first original article measuring opiorphin in a pain disorder.
Clinical relevance
Opiorphin may be a measurable biomarker for chronic pain, which could help in objectifying otherwise exclusively a subjective experience. Increased opiorphin could serve as a universal objective indicator of painful conditions. Since opiorphin may also reflect emotional and socio-relational imbalances occurring with BMS, it could as well represent a biomarker for BMS. Knowledge on opiorphin’s involvement in pain pathways could contribute to developing new clinical diagnostic methods for BMS.
Similar content being viewed by others
References
Wisner A, Dufour E, Messaoudi M, Nejdi A, Marcel A, Ungeheuer MN, Rougeot C (2006) Human opiorphin, a natural antinociceptive modulator of opioid-dependent pathways. Proc Natl Acad Sci U S A 103:17979–17984
Rougeot C, Robert F, Menz L, Bisson JF, Messaoudi M (2010) Systemically active human opiorphin is a potent yet non-addictive analgesic without drug tolerance effects. J Physiol Pharmacol 61:483–490
Javelot H, Messaoudi M, Garnier S, Rougeot C (2010) Human opiorphin is a naturally occurring antidepressant acting selectively on enkephalin-dependent delta-opioid pathways. J Physiol Pharmacol 61:355–362
Popik P, Kamysz E, Kreczko J, Wróbel M (2010) Human opiorphin: the lack of physiological dependence, tolerance to antinociceptive effects and abuse liability in laboratory mice. Behav Brain Res 213:88–93
Yang QZ, SS L, Tian XZ, Yang AM, Ge WW, Chen Q (2011) The antidepressant-like effect of human opiorphin via opioid-dependent pathways in mice. Neurosci Lett 489:131–135
Tian XZ, Chen J, Xiong W, He T, Chen Q (2009) Effects and underlying mechanisms of human opiorphin on colonic motility and nociception in mice. Peptides 30:1348–1354
Kamysz E, Sałaga M, Sobczak M, Kamysz W, Fichna J (2013) Characterization of the effects of opiorphin and sialorphin and their analogs substituted in position 1 with pyroglutamic acid on motility in the mouse ileum. J Pept Sci 19:166–172
Dufour E, Villard-Saussine S, Mellon V, Leandri R, Jouannet P, Ungeheuer MN, Rougeot C (2013) Opiorphin secretion pattern in healthy volunteers: gender difference and organ specificity. Biochem Anal Biochem 2:136. doi:10.4172/2161-1009.1000136
Rougeot C (2014) Opiorphin peptide derivatives as potent inhibitors of enkephalin-degrading ectopeptidases. US patent US8642729 B2
Al-Saffar MT, Al-Sandook TA, Y-Taha M (2013) A possible new concept in the mechanism of action of local anesthesia. Am J Med Biol Res 1:134–137
Headache Classification Subcommittee of the International Headache Society (2013) The international classification of headache disorders: 3rd edition. Cephalalgia 33:629–808
Zakrzewska JM, Forssell H and Glenny AM (2005) Interventions for the treatment of burning mouth syndrome. Cochrane Database Syst Rev CD002779. doi:10.1002/14651858.CD002779
Scala A, Checchi L, Montevecchi M, Marini I, Giamberardino MA (2003) Update on burning mouth syndrome: overview and patient management. Crit Rev Oral Biol Med 14:275–291
Grushka M, Ching V, Epstein V (2006) Burning mouth syndrome. Adv Othorinolaryngol 63:278–287
Forsell H, Jääakeläinen S, Tenovuo O, Hinkka S (2002) Sensory dysfunction in burning mouth syndrome. Pain 99:41–47
Hagelberg N, Forsell H, Rinne JO, Scheinin H, Taiminen T, Aalto S, Luutonen S, Någren K, Jääskeläinen S (2003) Striatal dopamine D1 and D2 receptors in burning mouth syndrome. Pain 101:149–154
Nagler RM, Hershkovich O (2004) Sialochemical and gustatory analysis in patients with oral sensory complaints. J Pain 5:56–63
Granot M, Nagler RM (2005) Association between regional idiopathic neuropathy and salivary involvement as the possible mechanism for oral sensory complaints. J Pain 6:581–587
Jääskeläinen SK (2012) Pathophysiology of primary burning mouth syndrome. Clin Neurophysiol 123:71–77
Sabalić M, Brkljačić L, Salarić I, Alajbeg I, Jerić I, Nemet I (2012) Salivary opiorphin as a potential marker of oral disease. Book of abstracts of the 11th Biennial Congress of the European Association of Oral Medicine. Oral Dis 18(1, SI):21
Brkljačić L, Sabalić M, Salarić I, Jerić I, Alajbeg I, Nemet I (2011) Development and validation of a liquid chromatography-tandem mass spectrometry method for the quantification of opiorphin in human saliva. J Chromatogr B Analyt Technol Biomed Life Sci 879:3920–3926
World Health Organization (2014) WHO Collaborating Centre for Drug Statistics Methodology, ATC classification index with DDDs. Available at: http://www.whocc.no/atc_ddd_publications/atc_ddd_index/
World Health Organization (1992) International Statistical Classification of Diseases and Related Health Problems, 10th revision (ICD-10). Geneva: WHO. Version for 2015. Available at: http://apps.who.int/classifications/icd10/browse/2015/en
Netto FO, Diniz IM, Grossmann SM, de Abreu MH, do Carmo MA, Aguiar MC (2011) Risk factors in burning mouth syndrome: a case-control study based on patient records. Clin Oral Investig 15:571–575
Gurvits GE, Tan A (2013) Burning mouth syndrome. World J Gastroenterol 19:665–672
Bergdahl M, Bergdahl J (1999) Burning mouth syndrome: prevalence and associated factors. J Oral Pathol Med 28:350–354
Lopez-Jornet P, Molino Pagan D, Andujar Mateos P, Rodriguez Agudo C, Pons-Fuster A (2015) Circadian rhythms variation of pain in burning mouth syndrome. Geriatr Gerontol Int 15:490–495. doi:10.1111/ggi.12303
Morris KE, St Laurent CD, Hoeve RS, Forsythe P, Suresh MR, Mathison RD, Befus AD (2009) Autonomic nervous system regulates secretion of anti-inflammatory prohormone SMR1 from rat salivary glands. Am J Physiol Cell Physiol 296:C514–C524
Heckmann SM, Heckmann JG, HiIz MJ, Popp M, Marthol H, Neundörfer B, Hummel T (2001) Oral mucosal blood flow in patients with burning mouth syndrome. Pain 90:281–286
Ran HH, Zhang R (2011) Renin-angiotensin system modulates vasoreactivity through a mechanism of oxidative stress. Sheng Li Ke Xue Jin Zhan 42:117–120
Fang Y, Li S, Zhou H, Tian X, Lv S, Chen Q (2014) Opiorphin increases blood pressure of conscious rats through renin-angiotensin system (RAS). Peptides 55C:47–51
Tian XZ, Chen Y, Bai L, Luo P, XJ D, Chen Q, Tian XM (2015) Effects and underlying mechanisms of human opiorphin on cardiovascular activity in anesthetized rats. Eur J Pharmacol 749:32–38
Salort-Llorca C, Mínguez-Serra MP, Silvestre FJ (2008) Drug-induced burning mouth syndrome: a new etiological diagnosis. Med Oral Patol Oral Cir Bucal 13:E167–E170
Mathison R, Davison JS, Befus AD (1994) Neuroendocrine regulation of inflammation and tissue repair by submandibular gland factors. Immunol Today 15:527–532
Mathison RD, Davison JS, St Laurent CD, Befus AD (2012) Autonomic regulation of anti-inflammatory activities from salivary glands. Chem Immunol Allergy 98:176–195
Mathison RD, Davison JS, Befus AD, Gingerich DA (2010) Salivary gland derived peptides as a new class of anti-inflammatory agents: review of preclinical pharmacology of C-terminal peptides of SMR1 protein. J Inflamm (Lond) 7:49
Rosinski-Chupin I, Huaulme JF, Rougeot C, Rougeon F (2001) The transcriptional response to androgens of the rat VCSA1 gene is amplified by both binary and graded mechanisms. Endocrinology 142:4550–4559
Woda A, Dao T, Gremeau-Richard C (2009) Steroid dysregulation and stomatodynia (burning mouth syndrome). J Orofac Pain 23:202–210
Kim HI, Kim YY, Chng JY, Ko JY, Kho HS (2012) Salivary cortisol, 17β-estradiol, progesterone, dehydroepiandrosterone, and α-amylase in patients with burning mouth syndrome. Oral Dis 18:613–620
Trombelli L, Mandrioli S, Zangari F, Saletti C, Calura G (1992) Oral symptoms in the climacteric. A prevalence study. Minerva Stomatol 41:507–513
Srivastava A, Wang J, Zhou H, Melvin JE, Wong DT (2008) Age and gender related differences in human parotid gland gene expression. Arch Oral Biol 53:1058–1070
Acknowledgements
We thank Lidija Brkljačić for her assistance with sample processing and LC-MS/MS analysis.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
Author Ivan Salarić declares that he has no conflict of interest. Author Maja Sabalić declares that she has no conflict of interest. Author Ivan Alajbeg declares that he has no conflict of interest.
Funding
The work was supported by the Croatian Science Foundation grant no. 3070 (“The role of oxidative stress and opiorphin in temporomandibular disorders,” PI: Assoc. Prof. Iva Alajbeg).
Ethical approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the Institutional Ethical Committee and with the 1964 Helsinki Declaration and its later amendments.
Informed consent
Informed consent was obtained from all individual participants included in the study. All pertaining data (de-identified medical data on study subjects, institutional ethical committee approval, copies of signed informed consent forms, laboratory results) can be obtained from the authors on request.
Rights and permissions
About this article
Cite this article
Salarić, I., Sabalić, M. & Alajbeg, I. Opiorphin in burning mouth syndrome patients: a case-control study. Clin Oral Invest 21, 2363–2370 (2017). https://doi.org/10.1007/s00784-016-2031-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00784-016-2031-9