title: Neuropeptide effects in the trigeminal system: pathophysiology and clinical       relevance in migraine.
abstract: The neuropeptides substance P, calcitonin gene-related peptide (CGRP) and vasoactive       intestinal polypeptide (VIP) have been considered as important mediators in migraine and other       primary headaches. CGRP and VIP have been found at increased concentrations in jugular venous       plasma during attacks of migraine or cluster headache, and CGRP receptor antagonists have       recently been shown to be effective in migraine therapy. Substance P and CGRP are produced       from a subset of trigeminal afferents, whereas VIP derives from parasympathetic efferents.       Release of these neuropeptides in the meninges can cause arterial vasodilatation, mast cell       degranulation and plasma extravasation in animal experiments, but only CGRP seems to be       relevant in migraine. Animal models have confirmed the important role of CGRP in meningeal       nociception. The activity of spinal trigeminal neurons is a sensitive integrative measure of       trigeminal activity and is partly under the control of CGRP, most likely via central       mechanisms. CGRP released from central terminals of trigeminal afferents in the spinal       trigeminal nucleus seems to facilitate nociceptive transmission via presynaptic mechanisms.       The central effect of CGRP is substantiated by suppression of nociceptive c-fos activation and       neuronal activity in the spinal trigeminal nucleus following CGRP receptor inhibition. These       proposed functions are supported by the localization of CGRP receptor components in the rat       cranial dura mater, trigeminal ganglion and spinal trigeminal nucleus. The currently available       data indicate multiple sites of CGRP action in trigeminal nociception and the pathogenesis of       migraine; however, central CGRP receptors are likely to be the essential targets in the       treatment of migraine using CGRP receptor antagonists.
authors: Institute of Physiology and Pathophysiology, University of Erlangen-Nuernberg, Erlangen, Germany. Messlinger@physiologie1.uni-erlangen.de
authors: Karl
authors: K
authors: Messlinger
authors: Michael J M
authors: MJ
authors: Fischer
authors: Jochen K
authors: JK
authors: Lennerz
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology*; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D004388:Dura Mater / Q000378:metabolism; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D008881:Migraine Disorders / Q000378:metabolism / Q000503:physiopathology*; D015288:Neurokinin A / Q000502:physiology; D009478:Neuropeptide Y / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000378:metabolism; D013373:Substance P / Q000378:metabolism / Q000502:physiology*; D012668:Trigeminal Ganglion / Q000503:physiopathology*; D014279:Trigeminal Nucleus, Spinal / Q000187:drug effects; D014660:Vasoactive Intestinal Peptide / Q000502:physiology*
chemical_list: D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D009478:Neuropeptide Y; D010879:Piperazines; D011799:Quinazolines; D018015:Receptors, Calcitonin Gene-Related Peptide; D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D015288:Neurokinin A; D015740:Calcitonin Gene-Related Peptide; C406305:olcegepant