Anti-CGRP monoclonal antibodies in cluster headache: what can we learn from recent clinical trials

Excerpt

Calcitonin gene-related peptide (CGRP) is considered a key molecule in the pathophysiology of cluster headache (CH). Sensory neurons in the trigeminal ganglion are rich in CGRP and release it upon stimulation. The CGRP released by unmyelinated trigeminal sensory neurons leads to the activation of Aδ meningeal nociceptive trigeminal fibers and modulates pain transmission in the trigeminocervical complex (TCC). This process takes place both in periphery (either inside the trigeminal ganglion or along the nerve trunk through axon-axon synapses) and inside the TCC. CGRP probably participates also in a connection between the trigeminal ganglion and the sphenopalatine ganglion. In humans, a clear link between the CGRP pathway and CH was first demonstrated by the observation of an increase in CGRP concentrations in the ipsilateral-to-the-pain external jugular vein during CH attacks. The subsequent administration of sumatriptan terminates the attack and simultaneously normalizes the CGRP plasma levels. Further, the intravenous infusion of CGRP can induce CH attacks in patients with active CH (i.e., episodic in-bout and chronic CH). …