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Time-course of pain and salivary opiorphin release in response to oral capsaicin differ in burning mouth syndrome patients, temporomandibular disorders patients and control subjects

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Abstract

Objectives

Opiorphin is an analgesic peptide released by salivary glands and capsaicin an agonist of TRPV1 receptors eliciting burning sensations. The primary objective of this study was to assess opiorphin release after stimulation of the tongue by capsaicin (STC). The secondary objectives were to compare opiorphin release after STC in 3 groups of subjects [healthy (CTRL), Burning Mouth Syndrome (BMS), painful Temporomandibular disorders (TMDp)] and pain evoked by STC in these 3 groups.

Materials and methods

Salivary opiorphin was assessed with high-performance liquid chromatography at 3 different time points (baseline, after 5 min and 20 min of STC). Pain was self-reported on a (0–10) numeric rating scale.

Results

Three groups (N = 16) of adults were recruited at the Clinical Hospital Centre and School of Dental Medicine in Zagreb. Opiorphin levels were higher (1) in TMDp compared to CTRL in 1st (2.23 ± 1.72 pg/ul vs. 0.67 ± 0.44 pg/ul, p = 0.002) and 3rd sampling (2.44 ± 2.01 pg/ul vs. 0.74 ± 0.52 pg/ul, p = 0.020) and (2) within BMS group at 3rd sampling vs. baseline (p < 0.025). Pain scores were higher in BMS compared to TMDp (p < 0.025) and CTRL (p < 0.025).

Conclusion

This study evidenced (1) a differential basal amount of opiorphin in two pain conditions and control subjects (2) a differential kinetic of release of opiorphin after STC in CTRL, BMS and TMDp (3) a differential pain perception after STC in BMS and TMDp vs. CTRL, which can provide a readout for animal models.

Clinical relevance

The specific regulation of opiorphin release in patients with orofacial painful conditions provides valuable insights for clinicians and researchers in physiology and pathology and encourages further research in this area.

Trial registration

ClinicalTrials.gov NCT04694274. Registered on 01/05/2021.

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Data availability

All data associated with this study are presented in the paper.

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Acknowledgements

This research was funded by the Croatian Science Foundation Project “Genetic polymorphisms and their association with temporomandibular disorders”, grant number [IP-2019-04-6211] and by LabNOF recurrent funding.

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Author notes

  1. Iva Z Alajbeg and Yves Boucher contributed equally to this work.

Authors and Affiliations

  1. Department of Removable Prosthodontics, University of Zagreb School of Dental Medicine, University of Zagreb, Zagreb, 10000, Croatia

    Iva Z. Alajbeg, Ema Vrbanovic, Ivan Orabovic, Klara Naka & Antonija Mrla

  2. Department of Oral Medicine, University of Zagreb School of Dental Medicine, University of Zagreb, Zagreb, 10000, Croatia

    Ivan Alajbeg

  3. Laboratoire de Neurobiologie Orofaciale, UFR Odontologie, Université Paris Cité, Paris, 75006, France

    Yves Boucher

  4. Department of Dental Medicine, Clinical Hospital Centre Zagreb, Zagreb, 10000, Croatia

    Iva Z. Alajbeg & Ivan Alajbeg

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Contributions

I.Z.A. conducted the research, wrote the manuscript, performed statistical analysis of the data, interpreted the results, managed the Croatian team and workflow, coordinated the analytical laboratory, and recruited TMD patients. E.V. wrote the manuscript, conducted the clinical portion of the experiment, recruited TMD patients, and presented the results. I.A. established the clinical portion of the experiment, recruited BMS patients, and provided research guidance. I.O. conducted the clinical portion of the experiment, presented the results, and analyzed the data. K.N. conducted the clinical portion of the experiment and presented the results. A.M. conducted the clinical portion of the experiment. Y.B. conceived the idea, designed and conceptualized the study, wrote a major part of the manuscript, and edited it. All authors reviewed the manuscript.

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Correspondence to Iva Z. Alajbeg.

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Alajbeg, I.Z., Vrbanovic, E., Alajbeg, I. et al. Time-course of pain and salivary opiorphin release in response to oral capsaicin differ in burning mouth syndrome patients, temporomandibular disorders patients and control subjects. Clin Oral Invest 28, 246 (2024). https://doi.org/10.1007/s00784-024-05653-y

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