“To our knowledge, ours is the first study to demonstrate that peroxynitrite contributes to stress-induced increases in painlike hypersensitivity, neuronal excitability and mitochondrial activity - all of which provide a basic framework for how peroxynitrite may be involved in these underlying mechanisms of migraine,” Dussor said. Gregory Dussor, Eugene McDermott Professor and department chair of neuroscience in the School of Behavioral and Brain Sciences “To our knowledge, ours is the first study to demonstrate that peroxynitrite contributes to stress-induced increases in painlike hypersensitivity, neuronal excitability and mitochondrial activity.”ĭr. The research has also identified additional effects of peroxynitrite. “Our data indicate a novel role for peroxynitrite in contributing to the development and maintenance of pain-like hypersensitivity in this preclinical model of migraine headache and point to a therapeutic target,” Dussor said. Subsequent research will investigate if targeting peroxynitrite will work safely in humans. After neutralizing the peroxynitrite that was produced in the mice, the team observed a decrease in facial hypersensitivity, a preclinical measure of pain. In the current study, UT Dallas researchers exposed mice to two common triggers of migraine in humans: repeated stress and a chemical that produces nitric oxide, also called a nitric oxide donor. “Can we safely inhibit a relevant pathway?” “We have to look at what happens after nitric oxide is produced,” Dussor said. Dussor and his team instead are investigating peroxynitrite - a reactive chemical that is produced in the body when nitric oxide reacts with other molecules - as a potential migraine cause. While inhibiting production of nitric oxide has been shown to help with migraine, it also raises blood pressure, which rules it out as a pharmaceutical solution. The body quickly breaks down nitroglycerin to nitric oxide, which causes the smooth muscle in blood vessels to relax, allowing more blood to flow through arteries and veins. Medically, nitroglycerin is a vasodilatory drug approved by the Food and Drug Administration to treat the chest pain caused by coronary artery disease. If we discover what it is, we might have a good drug target.” “It’s one of the first pharmacological migraine triggers ever documented, and it’s a robust, consistent phenomenon. “We’ve known for a long time that when you give migraine patients a compound that generates nitric oxide, such as nitroglycerin, it triggers a migraine attack in a very large number of them,” he said.
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