Migraine: How the release of nitric oxide can trigger headaches

Evan Walker
Evan Walker TheMediTary.Com |
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Researchers are looking into how nitric oxide releases may trigger migraine headaches. Vladimir Vladimirov/Getty Images
  • Researchers have found that among the most dependable methods to induce migraine headaches in experiments involve the use of substances that release nitric oxide.
  • However, the precise mechanisms through which nitric oxide triggers these attacks remain unclear.
  • It’s possible that reactive nitroxidative species, such as peroxynitrite, might be responsible.

Migraine is a health condition that leads to intense and repeating headaches, often accompanied by throbbing or pulsating sensations.

A migraine episode is a specific kind of headache. Typically, these episodes develop in phases and have the potential to extend over several days.

In more severe cases, they can have a substantial impact on a person’s everyday life, including their ability to carry out their daily activities.

Nitric oxide is a naturally occurring molecule in the body that serves various physiological functions, including vasodilation (widening of blood vessels), neurotransmission and immune response regulation.

In a medical context, there are instances where nitric oxide is intentionally administered as a therapeutic agent.

When a substance that releases nitric oxide is administered, it can trigger migraine headaches, but the exact mechanisms behind this is unclear.

There are some reactive substances in the body, such as nitric oxide and peroxynitrite, that seem to play a role in making pain sensations more sensitive and getting rid of peroxynitrite seems to reduce pain.

Now, in new research, published in the journal JNeurosci, researchers wanted to identify if peroxynitrite is involved in causing pain in two different models of migraine headaches.

The researchers used chemicals to reduce peroxynitrite, reporting that this lessened the increased pain sensitivity caused by stress and the nitric oxide-releasing substance, but it didn’t affect the increased sensitivity caused by the inflammatory substance.

These chemicals also helped to lower the levels of markers of peroxynitrite in the nerves and the tissue lining the brain. They also reduced the overactivity of nerves.

In addition, one of these chemicals seemed to help stressed male mice with their mitochondrial function (the energy production in cells) when exposed to the nitric oxide-releasing substance.

Experts say these findings strongly suggest that peroxynitrite is involved in causing migraines and suggest that targeting peroxynitrite could be a potential way to treat migraine.

Dr. Gregory Dussor, a professor and chair of the Department of Neuroscience at the University of Texas at Dallas and senior author of the study, spoke to Medical News Today.

“The primary finding of the work is that peroxynitrite, a reactive nitrogen species, seems to be an important contributor to the effects of nitric oxide in migraine,” he said.

Nitric oxide has been linked to migraine for over 150 years, ever since the discovery of nitroglycerin. Nitroglycerin works for chest pain by creating nitric oxide, but in doing so, it also triggers migraine attacks in susceptible individuals. Our work shows that this may happen through peroxynitrite that is created when nitric oxide reacts with other substances within the body, and not by nitric oxide itself.

Dr. Gregory Dussor

Dr. Huma Sheikh, an assistant professor of neurology at the Icahn-Mt Sinai School of Medicine and the chief executive officer of NY Neurology of Medicine who was not involved in this research, spoke to Medical News Today.

“This is an interesting article. I think it is helping to elucidate why nitric oxide is a trigger for migraine in some people.”

“It seems that the breakdown of this compound [peroxynitrite] is responsible for being a final trigger when the threshold is already low,” she said.

This may be why in migraine it can take a few triggers to finally start the migraine cascade. It is implicated that targeting [peroxynitrite] can be a way to help prevent migraine by either inhibiting this molecule or its after effects.

Dr. Huma Sheikh

Dussor said that “targeting peroxynitrite may be a new therapeutic approach for migraine.”

“While we know that nitric oxide is a problem in migraine, we can’t eliminate it because it would have very negative consequences for blood pressure regulation,” he explained.

“Unlike nitric oxide, peroxynitrite does not have a major role in regulating blood pressure. By targeting peroxynitrite, we may be able to treat migraine attacks but not change blood pressure,” Dussor added.

Ultimately, experts say, more research is needed.

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