Calcitonin Gene-Related Peptide (CGRP) Migraine Model

Calcitonin gene-related peptide (CGRP) is a key mediator of migraine pathophysiology and the target of several approved migraine therapeutics (CGRP receptor antagonists and monoclonal antibodies). CGRP promotes vasodilation of the middle meningeal artery and sensitizes neurons of the trigeminal nucleus caudalis, driving trigeminovascular activation and peripheral pain signaling.

Subcutaneous administration of CGRP in rats reproduces this pathophysiology, inducing cephalic (periorbital) mechanical allodynia, assessed by von Frey filaments, along with light-aversive behavior — a translational surrogate for the photophobia commonly reported by migraine patients. These effects parallel findings from human CGRP-provocation studies, supporting the model’s clinical relevance.

Pharmacological validation is provided by CGRP receptor antagonist rimegepant, which reverses CGRP-induced mechanical allodynia in rats, confirming the model’s specificity for the CGRP pathway.

Alongside the GTN and PACAP-38 paradigms, the CGRP model offers a complementary tool for characterizing candidates acting on distinct nodes of the trigeminovascular system, supporting mechanism-based positioning of novel anti-migraine compounds. For CGRP-mediated changes in dermal blood flow, see the capsaicin model.