Calcitonin gene-related peptide (CGRP) (CGRP)

Calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide that serves as a potent vasodilator and a key mediator in the transmission of pain, particularly within the trigeminovascular system (UniProt P06881; Russell et al., 2014). It is primarily released from capsaicin-sensitive primary afferent terminals, which are sensory neurons (C and A-delta fibers) that express the TRPV1 receptor (Messlinger, 2018). Upon release, CGRP binds to its receptor complex—composed of the calcitonin receptor-like receptor (CALCRL) and receptor activity-modifying protein 1 (RAMP1)—leading to increased cyclic AMP levels and subsequent vasodilation and neurogenic inflammation (Hay et al., 2018). This process is central to the pathophysiology of migraine, where CGRP levels are significantly elevated during attacks (Goadsby et al., 2017). Therapeutic interventions targeting CGRP include monoclonal antibodies that sequester the peptide, such as galcanezumab and fremanezumab, as well as small-molecule antagonists or antibodies that block its receptor (Tepper, 2018). These treatments aim to prevent the pro-nociceptive and vasodilatory effects of CGRP, providing effective prophylaxis and acute treatment for migraine and other headache disorders (Edvinsson et al., 2018).

Other names

alpha-CGRPbeta-CGRPCALCACALCBCalcitonin gene-related peptide 1Calcitonin gene-related peptide 2CGRP release

Monoclonal antibodies bind to and sequester the CGRP peptide, preventing its binding to the CGRP receptor complex (CALCRL/RAMP1), thereby inhibiting vasodilation and the transmission of pain signals in the trigeminovascular system.