Nitric oxide(NO) lead to vasodilation and is believed to be responsible in some instances for onset of certain types of migraines.(Drugs that dilate blood vessels can cause headaches, at least in some people.)
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 fulfills criteria for migraine without aura in migraine sufferers. Blockade of nitric oxide synthases (NOS) by L-NMMA effectively treats attacks of migraine without aura.