Nitric oxide in primary headaches

The molecular mechanisms that underlie the primary headaches-migraine, clus ter headache and tension-type headache-have not yet been clarified. On the basis of studies in headache induced by intravenous infusions of glyceryl t rinitrate (an exogenous nitric oxide donor) and histamine (which liberates nitric oxide from vascular endothelium), it has been suggested that nitric oxide is a likely candidate responsible molecule. The present review deals with the biology of this small messenger molecule, and the updated scientif ic evidence that suggests a key role for this molecule in primary headaches . This evidence suggests that the release of nitric oxide from blood vessel s, perivascular nerve endings or from brain tissue is an important molecula r trigger mechanism in spontaneous headache pain. Pilot trials have shown e fficacy of a nitric oxide synthase inhibitor in both migraine attacks and c hronic tension-type headache. These observations suggest new approaches to the pharmacological treatment of headache. Curr Opin Neurol 14:315-321. (C) 2001 Lippincott Williams & Wilkins.