The renin–angiotensin system: a possible contributor to migraine pathogenesis and prophylaxis

The presence of a tissue-based renin-angiotensin system, independent of the systemic one, has been identified in several organs including the brain. Experimental models have suggested the involvement of the renin-angiotensin system in neurogenic inflammation, susceptibility to oxidative stress, endothelial dysfunction, and neuromodulation of nociceptive transmission, thus potentially contributing to the pathogenesis of migraine. Genetic factors that increase susceptibility to migraine may include angiotensin-converting enzyme polymorphism, although available data are controversial. Clinical studies have suggested that angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may be effective in migraine prophylaxis. However, further research should clarify whether the postulated preventive effect is attributable to a pharmacological action over and above the antihypertensive effect and should test their tolerability in subjects with normal blood pressure values. In patients with contraindications or not responding to conventional prophylactic drugs and in patients with comorbid arterial hypertension, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may be used for migraine prophylaxis.