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

Inna E Tchivileva; Kirk W Johnson; Xiyun Chai; Lyndsey R VanDam; Pei Feng Lim; Gary D Slade

doi:10.2147/JPR.S408044

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

J Pain Res. 2023 Jul 11:16:2331-2346. doi: 10.2147/JPR.S408044. eCollection 2023.

Authors

Inna E Tchivileva^{1

2}, Kirk W Johnson³, Xiyun Chai⁴, Lyndsey R VanDam³, Pei Feng Lim^{1

5}, Gary D Slade^{1

6}

Affiliations

¹ Center for Pain Research and Innovation, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
² Division of Oral and Craniofacial Health Sciences, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
³ Pain Research, Eli Lilly and Company, Indianapolis, IN, USA.
⁴ Precision Medicine Neuroscience, AbbVie, Chicago, IL, USA.
⁵ Division of Diagnostic Sciences, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁶ Division of Pediatric and Public Health, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

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: headache; musculoskeletal pain; neuropeptide; orofacial pain; temporomandibular joint disorders.

Grants and 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.