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.
Neurogenic inflammation is presumed to be an important factor in migraine pathophysiology, mediated by the activation of primary neurons, leading to the release of various pro-inflammatory neuropeptides and neurotransmitters such as Calcitonin Gene-Related Peptide (CGRP), substance P (SP), and vasoactive intestinal peptide (VIP).
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.
Conclusion We found no statistical association between familial aggregation of migraine and hypersensitivity to calcitonin gene-related peptide infusion in migraine without aura patients.
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.
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.
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.
Calcitonin gene-related peptide (CGRP) plays a key role in migraine, and variations in female sex hormones may affect CGRP sensitivity and/or production.
Current antimigraine drugs are believed, besides their direct vasoconstrictive effect, to inhibit calcitonin gene-related peptide (CGRP) release from trigeminal nerve endings during migraine.
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.
Calcitonin gene-related peptide (CGRP), a well-known migraine mediator, potentiated BzATP-evoked membrane permeability in WT as well as R192Q KI cultures, demonstrating its modulatory role on trigeminal sensory ganglia.
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).
<b>Background:</b> Calcitonin gene-related peptide (CGRP) is pivotal in the pathophysiology of migraine headaches and represents a promising target for migraine treatment.
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.
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.
Calcitonin gene-related peptide (CGRP), the most abundant neuropeptide in primary afferent sensory neurons, is strongly implicated in the pathophysiology of migraine headache, but its role in migraine is still equivocal.
The neuropeptide calcitonin gene-related peptide (CGRP), a potent vasoactive and a marker of trigeminal inflammation, has been considered as an important mediator in various types of migraine such as pure menstrual 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.
The development of the triptan class of serotonin 5-HT1B/1D/1F receptor agonists has advanced our understanding of the neurobiology of migraine pain, which subsequently resulted in the development of calcitonin gene-related peptide (CGRP) modulators that are now showing promise as acute and preventative anti-migraine agents.
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.