Cluster headache is a primary headache characterized by recurring excruciating pain and autonomic signs, leading to significant suffering and derangement of patients' life. Efficacious new preventive treatments are needed. The pathophysiology of cluster headache comprises mechanisms both in the peripheral and central nervous system, involving the trigeminovascular system, the trigemino-parasympathetic reflex, and central modulating systems. Calcitonin gene-related peptide (CGRP) has an active role throughout these systems. It is increased during spontaneous and provoked attacks, and itself can induce attacks. Recently, drugs against this neuropeptide have been developed for the treatment of different headache disorders. In particular, monoclonal antibodies vs CGRP as galcanezumab and fremanezumab have been tested in cluster headache, with promising results for the episodic form. Considering the relevance of central mechanisms in CH, drugs interfering with the CGRP pathway in the central nervous system can enlarge the therapeutic armamentarium against this highly disabling condition.
Keywords: CGRP; Calcitonin gene–related peptide; Cluster headache; Headache; Monoclonal antibodies.