Serum 3-Hydroxybutyrate is Expected to Serve as One of the Supportive Diagnostic Markers of Persistent Idiopathic Dentoalveolar Pain (PDAP)

Abstract

Background

Persistent idiopathic dentoalveolar pain (PDAP), previously referred to as atypical odontalgia, is a chronic dental pain that occurs without signs of pathology. PDAP is considered a diagnosis of exclusion, and its definition is currently under refinement and remains ambiguous. The metabolite known as 3-hydroxybutyrate (3HB) has garnered significant interest as a potential indicator for both depression and chronic psychogenic pain. We investigated the characteristics of patients with PDAP and hypothesized that serum 3HB could support the diagnosis of PDAP.

Subjects and Methods

Forty-one patients with PDAP and 167 patients with odontogenic toothache were investigated regarding depression and anxiety scales in addition to the general dental evaluation. Blood tests including high-sensitivity CRP, HbA1c, and 3HB were performed for all patients. Associations between PDAP and patients’ varying characteristics were investigated using hierarchical multivariate logistic regression analyses.

Results

There were more females, current smokers, patients with orofacial pain (such as temporomandibular joint pain, glossalgia, and headache), and people with elevated 3HB levels among patients with PDAP than among control participants. Multivariate logistic regression analyses predicting patients with PDAP identified the female sex (odds ratio [OR]: 4.16), current smoking (OR: 14.9), glossalgia (OR: 19.8) a high CES-D score (≥16) (OR: 5.98), and elevated serum 3HB (≥80 μmol/L) (OR: 18.4) factors significantly associated with PDAP.

Conclusion

Our results demonstrated that serum 3HB levels could be elevated in patients with PDAP compared to other types of odontogenic pain, although 3HB was not specific to PDAP. Based on our findings, five factors - female sex, current smoking, depressive tendencies, chronic orofacial pains, and high serum 3HB levels - could be useful for diagnosing PDAP.

Keywords:

• persistent idiopathic dentoalveolar pain
• atypical odontalgia
• 3-hydroxybutyrate
• temporomandibular disorder
• orofacial pain

Abbreviations

PDAP, persistent idiopathic dentoalveolar pain; ICOP, International Classification of Orofacial Pain; ICHD-3, Third edition of the International Headache Classification; 3HB, 3-hydroxybutyrate; CES-D, Center for Epidemiologic Studies Depression Scale; STAI, State-Trait Anxiety Inventory; VIF, The variance inflation factor; TMD, Temporomandibular disorder; TTH, Tension-type headache; SSRI, Selective serotonin reuptake inhibitors; SNRI, Serotonin noradrenaline reuptake Inhibitors; IRB, Institutional Review Board.

Data Sharing Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Ethics and Consent to Participate

The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of Hirosaki University Graduate School of Medicine (approval number 2022-205). This study protocol was approved by the Institutional Review Board (IRB). The hospital patient data we used in the study were anonymized per the recommendations of the governance of Hirosaki University Graduate School of Medicine. As the study comprised solely of data collected retrospectively by Tamaki Dental Clinic, the IRB waived informed consent. Caretakers, legal guardians, and relatives of the patients included in this study were given the opportunity to opt out of the study at any time.

Acknowledgments

We thank Dr. Tamaki M for contributing to the work done in Tamaki Dental Clinic.

Disclosure

The authors have no conflicts of interest to declare in this work.

Additional information

Funding

The authors received no specific funding for this work.