Nitric Oxide (NO) is a small, membrane-permeable gas located in endothelial cells, platelets, neutrophils, and the brain. The primary biologic function of NO is vasodilation. Although NO was first identified as an important messenger molecule in the cardiovascular system, it has now been shown to be a neuronal signal transmitter. Endogenous NO is synthesized on demand by the enzyme NO synthase (NOS).17
Preclinical evidence supports the possible role of NO in the pathophysiology of headache.10,18
NOS-containing nerve fibers (parasympathetic and primary sensory neurons) are located around cranial vessels.16 This suggests that during migraine NO may be released, contributing to vasodilation and the activation of primary sensory neurons of the trigeminovascular system (TGVS), which is associated with the sensation of headache pain.16,18
Clinical evidence also supports the possible role of NO in the pathophysiology of headache and the validity of NO inhibition as a therapeutic target for the treatment of migraine.16
In one study, intravenous infusion of nitroglycerin (NTG), which releases NO, induced headache in more than 60% of individuals susceptible to migraine.19
In another study, the NOS inhibitor (546C88[LNMAH]) was efficacious for the acute treatment of migraine, providing further support for NO inhibition as a target for the treatment of migraine.20
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16. Edvinsson L, Uddman R. Neurobiology in primary headaches. Brain
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2005;48:438–456.
17. Tassorelli C, Joseph SA, Buzzi MG, Nappi G. The effects
on the central nervous system of nitroglycerin — putative mechanisms and mediators. Prog
Neurobiol.
1999;57:607–624.
18. Olesen J, Thomsen LL, Lassen LH, Olesen IJ. The nitric
oxide hypothesis of migraine and other vascular headaches. Cephalalgia.
1995;15:94–100.
19. Olesen J, Iverson HK, Thomsen LL. Nitric oxide supersensitivity;
a possible molecular mechanism of migraine pain. Neuroreport. 1993;4:1027–1030.
20. Lassen LH, Ashina M. Christiansen I, et al. Nitric oxide
synthase inhibition: a new principle in the treatment of migraine attacks. Cephalalgia.
1998;18:27–32.
