Salivary CGRP can monitor the different migraine phases: CGRP (in)dependent attacks

CGRP plays a key role in the transmission and modulation of nociceptive signals and is a critical component in the pathogenesis of migraine.To assess saliva as a substrate to measure CGRP by comparing interictal levels in patients with episodic migraine and controls; and to evaluate CGRP's temporal profile during migraine attacks.This prospective observational pilot study included young women with episodic migraine and healthy controls. We monitored salivary CGRP-like immunoreactivity (CGRP-LI) during 30 consecutive days and during migraine attacks. We considered six timepoints for the analysis: interictal (72h headache free), preictal (PRE-24h before the attack), ictal (headache onset, after 2h, after 8h), postictal (POST-24h after the attack). CGRP levels were quantified by ELISA.44 women (22 with episodic migraine, 22 healthy controls) were recruited. Differences in interictal salivary levels of CGRP between patients and controls (Me [IQR]: 98.0 [80.3] (95% CI 56.6, 124.0) vs. 54.3 [44.0] (95% CI 42.2, 70.1) pg/mL, p = 0.034) were found. An increase in CGRP levels during migraine attacks was detected (pre:169.0 [95% CI 104.2-234.0]; headache onset: 247.0 [181.9-312.0]; after 2h: 143.0 [77.6-208.0]; after 8h: 169.0 [103.5-234.0], post: 173.0 [107.8-238.0]). Patients were classified as having CGRP-dependent (79.6%) and non-CGRP dependent migraine attacks (20.4%) according to the magnitude of change between preictal and ictal phase. Accompanying symptoms such as photophobia and phonophobia were significantly associated to the first group.Salivary CGRP-LI levels, which interictally are elevated in episodic migraine patients, usually increase during a migraine attack in the majority of patients. However, not every attack is CGRP-dependent, which in turn, might explain different underlying pathophysiology and response to treatment.