CGRP Receptor Antagonism and Migraine

• Published in: Neurotherapeutics Vol. 7; no. 2; pp. 164 - 175
• Main Authors: Edvinsson, Lars, Ho, Tony W.
• Format: Journal Article
• Language: English
• Published: New York Elsevier Inc 01.04.2010; Springer-Verlag; Springer Nature B.V
• Subjects: Animals; Annan klinisk medicin; Azepines - chemistry; Azepines - therapeutic use; Biomedical and Life Sciences; Biomedicine; Calcitonin Gene-Related Peptide - metabolism; Calcitonin Gene-Related Peptide Receptor Antagonists; CGRP; CGRP receptor antagonists; Clinical Medicine; Dipeptides - chemistry; Dipeptides - therapeutic use; Humans; Imidazoles - chemistry; Imidazoles - therapeutic use; Klinisk medicin; Medical and Health Sciences; Medicin och hälsovetenskap; Migraine; Migraine Disorders - drug therapy; Migraine Disorders - metabolism; Nervous system; Neurobiology; Neurology; Neurosciences; Neurosurgery; Neurotransmitter Agents - metabolism; Other Clinical Medicine; Piperazines; Quinazolines - chemistry; Quinazolines - therapeutic use; Review; Review Article; trigeminovascular; trigeminovascular; CGRP receptor antagonists; CGRP; Migraine
• ISSN: 1933-7213; 1878-7479; 1878-7479
• DOI: 10.1016/j.nurt.2010.02.004

Calcitonin gene-related peptide (CGRP) is expressed throughout the central and peripheral nervous systems, consistent with control of vasodilatation, nociception, motor function, secretion, and olfaction. αCGRP is prominently localized in primary spinal afferent C and AΔ fibers of sensory ganglia, and βCGRP is the main isoform in the enteric nervous system. In the CNS there is a wide distribution of CGRP-containing neurons, with the highest levels occurring in striatum, amygdala, colliculi, and cerebellum. The peripheral projections are involved in neurogenic vasodilatation and inflammation, and central release induces hyperalgesia. CGRP is released from trigeminal nerves in migraine. Trigeminal nerve activation results in antidromic release of CGRP to cause non-endothelium-mediated vasodilatation. At the central synapses in the trigeminal nucleus caudalis, CGRP acts postjunctionally on second-order neurons to transmit pain signals centrally via the brainstem and midbrain to the thalamus and higher cortical pain regions. Recently developed CGRP receptor antagonists are effective at aborting acute migraine attacks. They may act both centrally and peripherally to attenuate signaling within the trigeminovascular pathway.