Plasma calcitonin gene-related peptide and nerve growth factor as headache and pain biomarkers in recently deployed soldiers with and without a recent concussion.

OBJECTIVE: The objective of this study was to characterize the utility of calcitonin gene-related peptide (CGRP) and nerve growth factor (NGF) as potential biomarkers for headache and pain disorders in the post-military deployment setting. BACKGROUND: The need to improve recognition, assessment, and prognoses of individuals with posttraumatic headache or other pain has increased interest in the potential of CGRP and NGF as biomarkers. METHODS: The Warrior Strong Study (NCT01847040) is an observational longitudinal study of United States-based soldiers who had recently returned from deployment to Afghanistan or Iraq from 2009 to 2014. The present nested cross-sectional analysis uses baseline data collected from soldiers returning to Fort Bragg, North Carolina. RESULTS: In total, 264 soldiers (mean (standard deviation [SD] age 28.1 [6.4] years, 230/264 [87.1%] men, 171/263 [65.0%] White) were analyzed. Mean (SD) plasma levels of CGRP were 1.3 (1.1) pg/mL and mean levels of NGF were 1.4 (0.4) pg/mL. Age was negatively correlated with NGF (-0.01 pg/mL per year, p = 0.007) but was not associated with CGRP. Men had higher mean (SD) CGRP plasma levels than women (1.4 95% confidence interval [CI; 1.2] vs. 0.9 95% CI [0.5] pg/mL, p < 0.002, Kruskal-Wallis test). CGRP levels were lower in participants who had a headache at the time of the blood draw (1.0 [0.6] pg/mL vs. 1.4 [1.2] pg/mL, p = 0.024). NGF was lower in participants with continuous pain (all types; 1.2 [0.4] vs. 1.4 [0.4] pg/mL, p = 0.027) and was lower in participants with traumatic brain injury (TBI) + posttraumatic headache (PTH) versus TBI without PTH (1.3 [0.3] vs. 1.4 [0.4] pg/mL, p = 0.021). Otherwise, CGRP and NGF were not associated with migraine-like headache, TBI status, or headache burden as measured by the number of medical encounters in crude or adjusted models. CONCLUSION: In this exploratory study, plasma levels of NGF and CGRP showed promise as biomarkers for headache and other types of pain. These findings need to be replicated in other cohorts.

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

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.