Objective:

To examine how Lars Edvinsson and Peter Goadsby’s work on calcitonin gene–related peptide (CGRP) redefined migraine pathophysiology and paved the way for the first targeted therapies. 

Background:

For much of the 20th century, migraine was viewed primarily as a vascular disorder, with pain attributed to vasodilation rather than neuronal dysfunction. The discovery of CGRP in the early 1980s reframed our understanding of migraine biology. Edvinsson localized CGRP to cranial vessels and sensory neurons, while Goadsby demonstrated its release during migraine attacks. Together, their findings established migraine as a neurovascular process within the trigeminovascular system, challenging decades of conventional thinking and laying the groundwork for a new therapeutic paradigm. 

Design/Methods:

A historical literature review was conducted using PubMed, Scopus, and Web of Science (1980–2024), with the search terms “CGRP,” “migraine,” “trigeminovascular,” and “monoclonal antibody.” 

Results:

In the early 2000s, CGRP infusion studies demonstrated a direct causal link between the peptide and migraine attacks. Early small-molecule CGRP receptor antagonists (gepants) established proof of concept but were limited by hepatotoxicity, prompting development of safer oral agents. The subsequent approval of monoclonal antibodies targeting CGRP or its receptor after 2018 represented a paradigm shift toward mechanism-based, prophylactic migraine therapy. This represents one of neurology’s clearest examples of how a molecular discovery can translate into targeted, mechanism-based care. 

Conclusions:

The evolution of CGRP research illustrates how meticulous scientific inquiry can overturn entrenched models and translate molecular discoveries into transformative clinical practice. Edvinsson and Goadsby’s contributions redefined migraine as a neurobiological disorder with identifiable, targetable pathways—ushering in a new era of rational, mechanism-driven therapy for headache medicine..