CGRP and Migraine: What Have We Learned From Measuring CGRP in Migraine Patients So Far?

Abstract

The multi-functional neuropeptide calcitonin gene-related peptide (CGRP) plays a major role in the pathophysiology of migraine. The detection of elevated CGRP levels during acute migraine headache was the first evidence of the importance of the peptide. Since then, elevated CGRP levels have been detected not only during spontaneous and experimentally induced migraine attacks but also interictally. However, the detection of CGRP in peripheral blood shows conflicting results. In this respect, alternative detection methods are needed and have been already proposed. This article summarizes what we have learned from studies investigating CGRP in jugular and peripheral blood and reviews the latest state of research concerning the detection of CGRP in saliva and tear fluid as well as their contribution to our understanding of migraine pathophysiology.

Keywords: calcitonin gene-related peptide; headache; migraine; neuropeptide; trigeminal system.

Figure 1

CGRP in the trigemino-vascular system. CGRP is released from peripheral afferents of the ophthalmic (V1), mandibular (V2) and maxillary (V3) division of the trigeminal nerve. Different studies showed elevated CGRP levels in saliva and tear fluid in ictal and interictal migraine patients (40). TG; trigeminal ganglion.

Figure 2

Primary afferents from the meninges and cerebral blood vessels reach the trigeminal ganglion, mostly through the ophthalmic branch (V1). The information is processed via first-order neurons in the TG to second-order neurons in the trigeminal nucleus caudalis forming the trigemino-cervical complex with C1 and C2 dorsal horns of the cervical spinal cord. The TCC projects to different areas in the brainstem (not outlined in this figure) and the thalamus. The activation of the TCC might also activate the trigeminal autonomic reflex. From the thalamus, nociceptive signals are conveyed to (sub-)cortical structures involved in pain perception (16). ACC, anterior cingulate cortex; AMY, amygdala; HYP, hypothalamus; INS, insula; PFC, prefrontal cortex; S1 and S2, somatosensory cortex; SPG, sphenopalatine ganglion; SSN, superior salivary nucleus; TCC, trigemino-cervical complex; TG, trigeminal ganglion; THA, thalamus; TNC, trigeminal nucleus caudalis.