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The role of nitric oxide (NO) in migraine, tension-type headache and cluster headache.
Pharmacol Ther. 2008 Nov; 120(2):157-71.P&T

Abstract

The most important primary headaches (i.e. independent disorders that are not caused by another disease) are migraine, tension-type headache and cluster headache. All primary headaches are in need of better treatments. Migraine has a prevalence of 10% in the general population and its societal costs are high. Although the precise mechanisms underlying the pathophysiology of migraine are still elusive, the last decades have witnessed some progress (e.g. involvement of serotonin, calcitonin gene-related peptide, nitric oxide, etc). Nitric oxide (NO) is a very important molecule in the regulation of cerebral and extra cerebral cranial blood flow and arterial diameters. It is also involved in nociceptive processing. Glyceryl trinitrate (GTN), a pro-drug for NO, causes headache in normal volunteers and a so called delayed headache that fulfils criteria for migraine without aura in migraine sufferers. Blockade of nitric oxide synthases (NOS) by L-NMMA effectively treats attacks of migraine without aura. Similar results have been obtained for chronic tension-type headache and cluster headache. Inhibition of the breakdown of cGMP also provokes migraine in sufferers, indicating that cGMP is the effector of NO-induced migraine. Several relationships exist between NO, calcitonin gene-related peptide and other molecules important in migraine. Also ion channels, particularly the K(ATP) channels, are important for the action of NO. In conclusion, inhibition of NO production or blockade of steps in the NO-cGMP pathway or scavenging of NO may be targets for new drugs for treating migraine and other headaches. Indeed, selective n-NOS and i-NOS inhibitors are already in early clinical development.

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Authors+Show Affiliations

Olesen J
University of Copenhagen, Department of Neurology, Glostrup Hospital, Ndr. Ringvej 57, DK - 2600 Glostrup, Copenhagen, Denmark. jeol@glo.regionh.dk

MeSH

AnimalsCalcitonin Gene-Related PeptideCluster HeadacheCyclic GMPDrug Delivery SystemsHumansIon ChannelsMigraine DisordersNitric OxideNitric Oxide Synthase Type INitric Oxide Synthase Type IITension-Type Headache

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

18789357

Clinical Trial Links

Understanding the Pathophysiology of Migraine Pain

Citation

Olesen, Jes. "The Role of Nitric Oxide (NO) in Migraine, Tension-type Headache and Cluster Headache." Pharmacology & Therapeutics, vol. 120, no. 2, 2008, pp. 157-71.
Olesen J. The role of nitric oxide (NO) in migraine, tension-type headache and cluster headache. Pharmacol Ther. 2008;120(2):157-71.
Olesen, J. (2008). The role of nitric oxide (NO) in migraine, tension-type headache and cluster headache. Pharmacology & Therapeutics, 120(2), 157-71. https://doi.org/10.1016/j.pharmthera.2008.08.003
Olesen J. The Role of Nitric Oxide (NO) in Migraine, Tension-type Headache and Cluster Headache. Pharmacol Ther. 2008;120(2):157-71. PubMed PMID: 18789357.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The role of nitric oxide (NO) in migraine, tension-type headache and cluster headache. A1 - Olesen,Jes, Y1 - 2008/08/23/ PY - 2008/08/01/received PY - 2008/08/01/accepted PY - 2008/9/16/pubmed PY - 2009/1/28/medline PY - 2008/9/16/entrez SP - 157 EP - 71 JF - Pharmacology & therapeutics JO - Pharmacol Ther VL - 120 IS - 2 N2 - The most important primary headaches (i.e. independent disorders that are not caused by another disease) are migraine, tension-type headache and cluster headache. All primary headaches are in need of better treatments. Migraine has a prevalence of 10% in the general population and its societal costs are high. Although the precise mechanisms underlying the pathophysiology of migraine are still elusive, the last decades have witnessed some progress (e.g. involvement of serotonin, calcitonin gene-related peptide, nitric oxide, etc). Nitric oxide (NO) is a very important molecule in the regulation of cerebral and extra cerebral cranial blood flow and arterial diameters. It is also involved in nociceptive processing. Glyceryl trinitrate (GTN), a pro-drug for NO, causes headache in normal volunteers and a so called delayed headache that fulfils criteria for migraine without aura in migraine sufferers. Blockade of nitric oxide synthases (NOS) by L-NMMA effectively treats attacks of migraine without aura. Similar results have been obtained for chronic tension-type headache and cluster headache. Inhibition of the breakdown of cGMP also provokes migraine in sufferers, indicating that cGMP is the effector of NO-induced migraine. Several relationships exist between NO, calcitonin gene-related peptide and other molecules important in migraine. Also ion channels, particularly the K(ATP) channels, are important for the action of NO. In conclusion, inhibition of NO production or blockade of steps in the NO-cGMP pathway or scavenging of NO may be targets for new drugs for treating migraine and other headaches. Indeed, selective n-NOS and i-NOS inhibitors are already in early clinical development. SN - 0163-7258 UR - https://www.unboundmedicine.com/medline/citation/18789357/The_role_of_nitric_oxide__NO__in_migraine_tension_type_headache_and_cluster_headache_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0163-7258(08)00141-1 DB - PRIME DP - Unbound Medicine ER -