Cluster headache is a trigeminal autonomic cephalalgia characterised by excruciatingly painful headache attacks, strictly unilateral, of short-lasting duration accompanied by ipsilateral autonomic symptoms and/or the sense of restlessness and agitation. Severity of pain attacks affects patient’s quality of life and, in some cases, might suggest suicidal ideation. Cluster headache is believed to take origin from an abnormal activity in the hypothalamus, the trigeminovascular system, and the autonomic nervous system. The hypothalamus plays a key role as generator or in producing permissive state starting a cluster period and or an episode; the peripheral nervous system is involved in pain. The most effective drug to treat an acute cluster headache attack is sumatriptan, a 5HT1B/D agonist. Monoclonal antibodies against calcitonin gene-related peptide, a fundamental neurotransmitter of the trigeminal system, seem to be effective as preventative treatment of cluster headache. Other studies will be discussed in order to stimulate and increase the understanding of the disorder and discuss other therapeutic targets.
Treatment of neurovascular headaches are in a new era thanks to the development of drugs targeting calcitonin gene-related peptide (CGRP) or its receptor. CGRP is one the main trigeminal sensory neuropeptides. Several of these drugs are waiting approval for use in migraine in 2018 and 2019. In the trigeminal ganglion, CGRP is expressed in C-fibres and its receptor is expressed in Aδ-fibres; these types of fibres are involved in different aspects of pain perception. Calcitonin gene-related peptide (CGRP) has been shown to increased during acute migraine attacks in multiple studies The trigeminal ganglion plays a key role in triggering the trigeminovascular reflex, aimed to protect against vasoconstriction; activation of the trigeminovascular system, followed by CGRP release, leads to the perception of pain in migraine. Since the trigeminal ganglion and dura are not protected by the blood–brain barrier, they are easily targeted by gepants and antibodies in neurovascular headache treatment. CGRP receptor antagonists, anti-CGRP antibodies and anti-CGRP receptor antibodies have proved effective for migraine and partly for cluster headache pain relief. These studies clearly support the central role that CGRP in migraine and neurovascular headaches pathophysiology.
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