TY - JOUR
T1 - Molecular Mechanisms of Migraine
T2 - Nitric Oxide Synthase and Neuropeptides
AU - Karsan, Nazia
AU - Gosalia, Helin
AU - Goadsby, Peter J.
N1 - Publisher Copyright:
© 2023 by the authors.
PY - 2023/8
Y1 - 2023/8
N2 - Migraine is a common condition with disabling attacks that burdens people in the prime of their working lives. Despite years of research into migraine pathophysiology and therapeutics, much remains to be learned about the mechanisms at play in this complex neurovascular condition. Additionally, there remains a relative paucity of specific and targeted therapies available. Many sufferers remain underserved by currently available broad action preventive strategies, which are also complicated by poor tolerance and adverse effects. The development of preclinical migraine models in the laboratory, and the advances in human experimental migraine provocation, have led to the identification of key molecules likely involved in the molecular circuity of migraine, and have provided novel therapeutic targets. Importantly, the identification that vasoconstriction is neither necessary nor required for headache abortion has changed the landscape of migraine treatment and has broadened the therapy targets for patients with vascular risk factors or vascular disease. These targets include nitric oxide synthase (NOS) and several neuropeptides that are involved in migraine. The ability of NO donors and infusion of some of these peptides into humans to trigger typical migraine-like attacks has supported the development of targeted therapies against these molecules. Some of these, such as those targeting calcitonin gene-related peptide (CGRP), have already reached clinical practice and are displaying a positive outcome in migraineurs for the better by offering targeted efficacy without significant adverse effects. Others, such as those targeting pituitary adenylate cyclase activating polypeptide (PACAP), are showing promise and are likely to enter phase 3 clinical trials in the near future. Understanding these nitrergic and peptidergic mechanisms in migraine and their interactions is likely to lead to further therapeutic strategies for migraine in the future.
AB - Migraine is a common condition with disabling attacks that burdens people in the prime of their working lives. Despite years of research into migraine pathophysiology and therapeutics, much remains to be learned about the mechanisms at play in this complex neurovascular condition. Additionally, there remains a relative paucity of specific and targeted therapies available. Many sufferers remain underserved by currently available broad action preventive strategies, which are also complicated by poor tolerance and adverse effects. The development of preclinical migraine models in the laboratory, and the advances in human experimental migraine provocation, have led to the identification of key molecules likely involved in the molecular circuity of migraine, and have provided novel therapeutic targets. Importantly, the identification that vasoconstriction is neither necessary nor required for headache abortion has changed the landscape of migraine treatment and has broadened the therapy targets for patients with vascular risk factors or vascular disease. These targets include nitric oxide synthase (NOS) and several neuropeptides that are involved in migraine. The ability of NO donors and infusion of some of these peptides into humans to trigger typical migraine-like attacks has supported the development of targeted therapies against these molecules. Some of these, such as those targeting calcitonin gene-related peptide (CGRP), have already reached clinical practice and are displaying a positive outcome in migraineurs for the better by offering targeted efficacy without significant adverse effects. Others, such as those targeting pituitary adenylate cyclase activating polypeptide (PACAP), are showing promise and are likely to enter phase 3 clinical trials in the near future. Understanding these nitrergic and peptidergic mechanisms in migraine and their interactions is likely to lead to further therapeutic strategies for migraine in the future.
KW - calcitonin gene related peptide
KW - migraine
KW - neuropeptide
KW - Neuropeptide Y
KW - nitric oxide
KW - pituitary adenylate cyclase activating polypeptide
KW - vasoactive intestinal peptide
UR - http://www.scopus.com/inward/record.url?scp=85167741756&partnerID=8YFLogxK
U2 - 10.3390/ijms241511993
DO - 10.3390/ijms241511993
M3 - Review article
C2 - 37569369
AN - SCOPUS:85167741756
SN - 1661-6596
VL - 24
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 15
M1 - 11993
ER -
