Abstrato

CGRP antagonists for the treatment of migraine: rationale and clinical data

Lars Edvinsson, Mattias Linde

CGRP is localized in primary spinal afferent C and Aδ fibers of the sensory ganglia and in the CNS, for example, in the colliculi and cerebellum. Trigeminal nerve activation results in antidromic release of CGRP that leads to vasodilatation via a CGRP-receptor complex (calcitonin-like receptor and RAMP1). At central synapses in the trigeminal nucleus caudalis, CGRP on second-order neurons transmits pain signals centrally. Calcitonin-like receptor and RAMP1 are widely expressed throughout the brain and in intracranial arteries and the trigeminal system. CGRP does not induce neurogenic inflammation or sensitization at peripheral meningeal sites, but relays nociceptive information to the second-order neurons in the brainstem. Recently developed CGRP-receptor antagonists have excellent antimigraine effects and a low side-effect profile. The CGRP-receptor antagonists reduce signaling in the trigeminovascular pathway at multiple sites and at central sites, however, the exact site of antimigraine effect is still under debate.