Calcitonin gene-related peptide (CGRP) plays a key role in migraine, and variations in female sex hormones may affect CGRP sensitivity and/or production.
Conclusion Our data show an unexpected 'positive' role for the endogenous pro-nociceptive migraine mediator CGRP, suggesting more careful examination of migraine prophylaxis strategy based on CGRP antagonism although it should be noted that homocysteine induced apoptosis in primary neuronal cell culture might not necessarily reproduce all the features of cell loss in the living organism.
Implications for therapeutic development have grown out of our understanding of migraine neurophysiology, leading to major drug classes, such as triptans, calcitonin gene-related peptide receptor antagonists, and 5-HT<sub>1F</sub> receptor agonists, as well as neuromodulatory approaches, with the promise of more to come.
However, a peripheral site of action is indicated by the ability of intravenous CGRP to trigger migraine in humans and the efficacy of CGRP receptor antagonists that evidently do no penetrate the CNS in effective amounts.
Understanding the biology of migraine through careful bench-based research has led to major classes of therapeutics being identified: triptans, serotonin 5-HT<sub>1B/1D</sub> receptor agonists; gepants, calcitonin gene-related peptide (CGRP) receptor antagonists; ditans, 5-HT<sub>1F</sub> receptor agonists, CGRP mechanisms monoclonal antibodies; and glurants, mGlu<sub>5</sub> modulators; with the promise of more to come.
The neuropeptide calcitonin gene-related peptide (CGRP) is found in afferent sensory nerve fibers innervating the resistance arteries and plays a pivotal role in a number of neurovascular diseases such as migraine and subarachnoid bleedings.
Currently, it is generally recognized that migraine headaches result from the activation and sensitization of trigeminal sensory afferent fibers leading to neuropeptides release such as calcitonin gene-related peptide (CGRP) and substance P (SP).
The recent identification of the CGRP-responsive calcitonin receptor/RAMP1 complex (AMY<sub>1</sub> receptor - amylin subtype 1 receptor) in the trigeminovascular system warrants a deeper consideration of the molecular identity of CGRP receptor(s) involved in the pathophysiology, and thus potential treatment of migraine.
Calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating peptide-38 (PACAP38) are endogenous neuropeptides that can trigger migraine attacks and have in recent years gained considerable interest in the migraine field.
Research shows that there are multiple areas of overlap between migraine pathophysiology and the central and peripheral pathways regulating feeding: inflammatory mediators such as the calcitonin gene-related protein (CGRP), neurotransmitters such as serotonin, peptides such as orexin and adipocytokines such as adiponectin (ADP) and leptin could explain the common pathogenesis.
We will further discuss the therapeutic agents which have appeared in the most recent years for migraine care, from calcitonin gene-related peptide (CGRP) receptor antagonists, gepants; through serotonin 5-HT<sub>1F</sub> receptor agonists, ditans, and CGRP or CGRP receptor monoclonal antibodies to invasive and non-invasive neuromodulation techniques.
Methods Following sumatriptan priming to model MOH, rats were hyper-responsive to environmental stress, demonstrating delayed cephalic and extracephalic allodynia and increased levels of CGRP in the jugular blood, consistent with commonly observed clinical outcomes during migraine.
Monoclonal antibodies to calcitonin gene-related peptide and its receptor (CGRP-mAbs) appear more promising for migraine because of considerably better effect and safety profiles.
In recent years the evidence on the role of calcitonin gene-related peptide (CGRP) in migraine pathophysiology has been consolidated, so new and promising treatments for migraine pain and its possible prevention have been developed.
Given the clear involvement of the neuropeptide CGRP in migraine and the emerging evidence for other peptides, it seems likely that neuropeptides may help "awaken" the senses and contribute to the heightened sensory state of migraine.
The inhibitor of AChE neostigmine did not change the firing <i>per se</i> but induced nociceptive activity, sensitive to d-tubocurarine, after pretreatment of meninges with the migraine mediator CGRP.