Revealed! What really triggers migraines

The molecular events that lead to debilitating migraines that afflict five million Australians every year have always been a mystery ... until now.

A 2021 study, published in the prestigious journal Science, was conducted by the Monash Institute of Pharmaceutical Sciences and the ARC Centre for Cryo-EM of Membrane Proteins.

One of the most common triggers for migraine is abnormal levels of activation of the target for an extremely potent vascular regulator, calcitonin gene-related peptide (CGRP). The newest and most exciting treatments act by blocking this activity, but how CGRP activates its receptor had never been demonstrated.

Lead author Dr Tracy Josephs said,

We showed that initial binding of CGRP to the receptor caused unexpectedly small conformational changes in the most prevalent form of the receptor. It was the coordinated change in dynamics of the external (CGRP binding) face of the receptor and the intracellular face that was the key.