Evaluation of Plasma Calcitonin Gene-Related Peptide as a Biomarker for Painful Temporomandibular Disorder and Migraine

Abstract

Objective

To assess associations of plasma calcitonin gene-related peptide (CGRP) with chronic temporomandibular disorder (TMD) myalgia/arthralgia or frequent/chronic migraine, alone and in combination, and to evaluate relations between the CGRP concentration and clinical, psychological, and somatosensory characteristics of participants.

Methods

The cross-sectional study selected four groups of adult volunteers: healthy controls (HCs), TMD without migraine, migraine without TMD, and TMD with migraine. Each group comprised 20 participants, providing 94% power to detect statistically significant associations with CGRP concentration for either TMD or migraine. TMD and headache were classified according to the Diagnostic Criteria for TMD and the International Classification for Headache Disorders, 3rd edition, respectively. Plasma CGRP was quantified with a validated high-sensitivity electrochemiluminescent Meso Scale Discovery assay. Questionnaires and clinical examinations were used to evaluate characteristics of TMD, headache, psychological distress, and pressure pain sensitivity. Univariate regression models quantified associations of the CGRP concentration with TMD, migraine, and their interaction. Univariate associations of the CGRP concentration with clinical, psychological, and pressure pain characteristics were also assessed.

Results

Among 80 participants enrolled, neither TMD nor migraine was associated with plasma CGRP concentration (P = 0.761 and P = 0.972, respectively). The CGRP concentration (mean ± SD) was similar in all 4 groups: HCs 2.0 ± 0.7 pg/mL, TMD 2.1 ± 0.8 pg/mL, migraine 2.1 ± 0.9 pg/mL, and TMD with migraine 2.2 ± 0.7 pg/mL. CGRP concentration was positively associated with age (P = 0.034) and marginally with body mass index (P = 0.080) but was unrelated to other participant characteristics.

Conclusion

In this well-powered study, interictal plasma concentration of CGRP was a poor biomarker for TMD and migraine.

Keywords:

• orofacial pain
• musculoskeletal pain
• neuropeptide
• temporomandibular joint disorders
• headache

Abbreviations

TMD, temporomandibular disorder; CGRP, calcitonin gene-related peptide; CNS, central nervous system; TMJ, temporomandibular joint; HCs, healthy controls; MIG, migraine group; DC/TMD, the Diagnostic Criteria for TMD; ICHD-3, the International Classification of Headache Disorders, 3rd edition; TTH, tension-type headache; BMI, body mass index; GCPS, Graded Chronic Pain Scale; JFLS, Jaw Functional Limitation Scale; HIT-6, Headache Impact Test-6; HADS, Hospital Anxiety and Depression Scale; PSS, Perceived Stress Scale; SCL-90R, Symptom Checklist 90-Revised; PPT, pressure pain threshold; SD, standard deviation; UNC-CH, University of North Carolina at Chapel Hill.

Acknowledgments

The authors wish to thank Dr. Shreya Nayak, the UNC-CH Orofacial Pain Program resident, and Sonya Capps, the study coordinator, for their valuable contribution to the study.

Author Contributions

All authors contributed to data analysis, drafting or revising the article, have agreed on the journal to which the article will be submitted, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

KWJ and LRV are employees of Eli Lilly and Company and may or may not hold stock in the company. XC is an employee of AbbVie. The authors report no other conflicts of interest in this work.

Additional information

Funding

Funding for this study was provided by the UNC-CH Adams School of Dentistry to IET. The sponsor was not involved in any stage of the project.