CGRP and migraine.

Abstract

Migraine has been estimated to be the seventh highest cause of disability worldwide, and the third most common disease worldwide after dental caries and tension type headache. However, the use of currently available acute and prophylactic medications to control this condition, such as 5-HT1 agonists (triptans) and beta-blockers, is limited by side effects and efficacy so that alternative and more specific treatments are required. More recently, an improved understanding of the pathophysiology of disease has allowed investigation of new therapeutic targets. The 37 amino acid neuropeptide calcitonin gene-related peptide (CGRP) has been shown to play a crucial role in the trigeminocervical complex pathway for nociception in the head. Studies have demonstrated elevated levels in the external jugular vein during the headache phase of migraine, with reduction following headache resolution. Furthermore, CGRP infusion triggers migraine type headache and subsequent treatment with triptans results in normalization of CGRP levels. This neuropeptide is therefore thought to have a central role in pain modulation as it participates in the neurovascular pathway and contributes to the vasodilation and neurogenic inflammation, which leads to migrainous attacks. Targeting CGRP may provide the ideal therapeutic tool needed for control of this common and debilitating illness. The three studies chosen for this month’s journal club are a small sample of the large amount of research being performed on CGRP. The first investigates whether its measurement can be used to classify migraine. The second and third articles are phase II clinical trials which investigate the use of CGRP antagonists and a monoclonal antibody CGRP