Salivary CGRP as diagnostic and migraine attack phase monitor biomarker: CGRP (in)dependent attacks

Abstract

ABSTRACTObjectiveTo assess saliva as a substrate to measure CGRP by comparing interictal levels of CGRP in patients with episodic migraine and controls; and to evaluate saliva CGRP temporal profile during migraine attacks.MethodsThis prospective observational study included women with episodic migraine and healthy controls. Participants collected daily saliva samples for 30 consecutive days and 3 additional ones during migraine attacks. 4 timepoints were considered: interictal (72h headache-free), preictal (PRE-24h before the attack), ictal (0h,2h,8h), postictal (POST-24h after the attack). CGRP levels were quantified by ELISA.Results35 women (22 patients, 13 controls) were included. Statistically significant differences were found in interictal salivary levels of CGRP between patients and controls (median[IQR]: 98.0 [86.7] vs. 42.2 [44.7] pg/mL; p=0.010). An increase in CGRP levels during migraine attacks was detected (median[IQR]: preictal 113.5 [137.8], 0h 164.6 [204.5], 2h 101.7 [159.1], 8h 82.6 [166.2], postictal 79.6 [124.3] pg/ml; p<0.001). Patients were classified as having CGRP-dependent (80.0%) and non-CGRP dependent migraine attacks (20.0%) according to the magnitude of change between preictal and ictal phase (0h). Accompanying symptoms were different depending on the type of attack. In the longitudinal analysis, we observed that the amount of CGRP measured during attacks were phase dependent and it was influenced by the frequency of monthly headache days (p=0.02).InterpretationPatients with episodic migraine have higher interictal salivary levels of CGRP than controls. These levels usually increase during a migraine attack, however, not every attack is CGRP-dependent, which in turn, might explain different underline pathophysiology and response to acute and preventive treatment.