Oxidative stress–mediated proapoptosis signaling: A novel theory on the mechanism underlying the pathogenesis of burning mouth syndrome

Shimrit Heiliczer*, Robert Yanko, Yair Sharav, Doron J. Aframian, Michael Klutstein, Asaf Wilensky, Yaron Haviv

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Background: Burning mouth syndrome (BMS) is a chronic oral pain disorder characterized by a generalized burning sensation in the oral mucosa without apparent medical or dental causes. Despite various hypotheses proposed to explain BMS pathogenesis, a clear understanding of the cellular-level events and associated histologic and molecular findings is lacking. Advancing our understanding of BMS pathogenesis could facilitate the development of more targeted therapeutic interventions. Types of Studies Reviewed: The authors conducted an extensive literature search and review of cellular mechanisms, focusing on evidence-based data that support a comprehensive hypothesis for BMS pathogenesis. The authors explored novel and detailed mechanisms that may account for the characteristic features of BMS. Results: The authors proposed that BMS symptoms arise from the uncontrolled activation of proapoptotic transmembrane calcium permeable channels expressed in intraoral mucosal nerve fibers. Elevated levels of reactive oxygen species or dysfunctional antiapoptosis pathways may lead to uncontrolled oxidative stress–mediated apoptosis signaling, resulting in upregulation of transmembrane transient receptor potential vanilloid type 1 and P2X 3 calcium channels in nociceptive fibers. Activation of these channels can cause nerve terminal depolarization, leading to generation of action potentials that are centrally interpreted as pain. Conclusions and Practical Implications: The authors present a novel hypothesis for BMS pathogenesis, highlighting the role of proapoptotic transmembrane calcium permeable channels and oxidative stress–mediated apoptosis signaling in the development of BMS symptoms. Understanding these underlying mechanisms could provide new insights into the development of targeted therapeutic interventions for BMS. Additional research is warranted to validate this hypothesis and explore potential avenues for effective management of BMS.

Original languageAmerican English
JournalJournal of the American Dental Association
Early online date15 Nov 2023
StateE-pub ahead of print - 15 Nov 2023

Bibliographical note

Publisher Copyright:
© 2023 American Dental Association


  • Burning mouth syndrome
  • calcium signaling
  • molecular mechanisms
  • oxidative stress
  • pathogenesis
  • proapoptosis signaling
  • reactive oxygen species


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