Identifying New Antimigraine Targets: Lessons from Molecular Biology. (April 2021)

• Record Type: Journal Article
• Authors: Edvinsson, Lars; Haanes, Kristian Agmund
• Is Part Of: Trends in pharmacological sciences. Volume 42:Number 4(2021)
• Page Start: 217
• Page End: 225
• Publication Date: 2021-04
• Subjects: calcitonin gene-related peptide -- node of Ranvier, Aδ fibers -- C fibers -- trigeminovascular system, G-protein coupled receptors; Pharmacology -- Periodicals; Pharmacology -- trends -- Periodicals; Pharmacologie -- Périodiques; Pharmacology; Electronic journals; Periodicals; 615.1
• DOI: 10.1016/j.tips.2021.01.002
• Languages: English
• ISSNs: 0165-6147

Abstract

Abstract : Primary headaches are one of the most common conditions; migraine being most prevalent. Recent work on the pathophysiology of migraine suggests a mismatch in the communication or tuning of the trigeminovascular system, leading to sensitization and the release of calcitonin gene-related peptide (CGRP). In the current Opinion, we use the up-to-date molecular understanding of mechanisms behind migraine pain, to provide novel aspects on how to modify the system and for the development of future treatments; acute as well as prophylactic. We explore the distribution and the expression of neuropeptides themselves, as well as certain ion channels, and most importantly how they may act in concert as modulators of excitability of both the trigeminal C neurons and the Aδ neurons. Highlights: Neuroimaging experiments propose that the migraine attack originates in the hypothalamus. A further mismatch in the communication or tuning of the trigeminovascular system, might lead to calcitonin gene-related peptide (CGRP) release, sensitization, and migraine pain. Potential targets for CGRP include the middle meningeal artery, satellite glial cells, and importantly Aδ neurons. The CGRP receptor is also expressed in the node of Ranvier, and the current hypothesis recognizes this novel site as a regulator of excitability. At the molecular level, new targets can be found among modulators of excitability, both on the C fibers (to prevent neuropeptide release) and on Aδ fibers (to reduce action potential generation and sensitization), with novel targets being GPCRs or ion channels localized at the node of Ranvier.