Nitric oxide theory of migraine.

The molecular mechanisms of migraine pain have not yet been clarified. Neurogenic inflammation and a subsequent plasma extravasation in the dura mater have been suggested. However, monoamine and peptide neurotransmitters involved in neurogenic inflammation do not cause significant head pain. Based on our previous studies of headache induced by i.v.infusions of glyceryl trinitrate (exogenous nitric oxide donor) and histamine (which liberates nitric oxide from vascular endothelium), we suggest that nitric oxide (NO) is a more likely candidate molecule. The present review deals with the biology of this small messenger molecule and the scientific evidence suggesting a key role for this molecule in migraine headache. We hypothesise that the release of NO from either blood vessels, perivascular nerve endings, or brain tissue is a molecule trigger mechanism of spontaneous migraine pain. These novel observations dictate new approaches to the pharmacological treatment of migraine.