Involvement of Calcitonin gene-related peptide （CGRP） in migraine

Abstract

　

　Calcitonin gene-related peptide (CGRP) is present virtually throughout the human body and found extensively in the central nervous system (CNS) , peripheral nervous, cardiovascular, and gastrointestinal systems. CGRP receptors are highly expressed in the trigeminovascular system and have been demonstrated in various sites such as the cell body of neurons and satellite glial cells of the trigeminal ganglion, meningeal mast cells as well as in the meningeal vasculature. CGRP and its receptor have also been demonstrated in the CNS in areas such as the trigeminal nucleus caudalis, brainstem nuclei, periaqueductal grey, thalamus, hypothalamus, and cerebellum. The significance of CGRP in the pathogenesis of migraine is evident by numerous experiments. Elevated levels of CGRP demonstrated in internal as well as external jugular venous blood during an episode of migraine and its normalization following administration of sumatriptan with alleviation of pain, suggested possibility of CGRP being crucial to the generation of migraine headache.　
　Recent development of anti-CGRP drugs and their substantial efficacy in the treatment and prophylaxis of migraine has facilitated in consolidating all the data obtained from previous research. The evolution of anti-CGRP antibodies has been a revolutionary step with significant implications in the field of migraine. The site of action of these drugs remains uncertain but it has been proposed that as monoclonal antibodies are large molecules that cannot cross the blood-brain barrier, they probably have a peripheral rather than central site of action in the nervous system. Potential sites would be the dura mater and the trigeminal ganglion where prominent actions of CGRP such as neurogenic inflammation and peripheral sensitization may be suppressed by the anti-CGRP monoclonal antibodies (mAbs) .
　Although speculation still surrounds the site of action of the anti-CGRP mAbs, with potential sites being the meninges and trigeminal ganglion, all clinical trials have consistently demonstrated the mAbs to be extremely efficacious in the prophylaxis of episodic as well chronic migraine by causing a significant decrease in the number of monthly migraine days, with negligible side-effects, which make these drugs more suitable than currently used drugs. The success of these drugs in migraine prophylaxis treatment has encouraged researchers in further investigating the pathophysiology of migraine.