Migraine is the most prevalent of the
neurological disorders and can affect the patient throughout the lifetime.
Calcitonin gene-related peptide (CGRP) is a
neuropeptide that is expressed in the central and peripheral nervous systems. It is now 2 decades since it was proposed to be involved in
migraine pathophysiology. The cranial sensory system contains C-fibers storing CGRP and trigeminal nerve activation and acute
migraine attacks result in release of CGRP. The
CGRP receptor consists of a complex of
calcitonin receptor-like receptor (CLR),
receptor activity-modifying protein 1 (RAMP1) and receptor component
protein (RCP). At the central synapses in the trigeminal nucleus caudalis, CGRP acts postjunctionally on second-order neurons to transmit
pain signals centrally via brainstem and midbrain to thalamus and higher cortical
pain regions. CLR and RAMPs are widely expressed throughout the brain, in the trigeminal ganglion and in intracranial arteries. CGRP does not induce
neurogenic inflammation or sensitization at peripheral meningeal sites but relays nociceptive information from trigeminal primary afferent neurons to the second-order neurons in the spinal trigeminal nucleus neurons.
CGRP receptor antagonists have been developed as novel antimigraine drugs and found to be effective in the treatment of acute
migraine attacks. Other ways to stop CGRP activity has been introduced recently through
antibodies against CGRP and the
CGRP receptor. While the
CGRP receptors are expressed both in the CNS and at various places related to the trigeminal system the exact site of action for their
therapy effect is still unresolved but the new approaches may resolve this.