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

Abstract

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.

Keywords::

• angiotensin converting enzyme
• angiotensin converting enzyme inhibitors
• angiotensin receptor blocker
• headache
• migraine

Financial & competing interests disclosure

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• There is a need for new drugs as those currently used for migraine prophylaxis are often discontinued due to limited efficacy or adverse effects.

• The brain has a local renin–angiotensin system (RAS) that plays an important role in several neurological diseases, such as epilepsy, cerebrovascular diseases, Parkinson’s disease and Alzheimer’s disease.

• The RAS is involved in migraine pathophysiology. Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), as drugs acting on this system, can play a major role in the prophylactic management of migraine.

• Preclinical studies suggest a link between the activation of the RAS and that of nociceptive systems in the brain.

• Genetic studies suggest a link between angiotensin-converting enzyme gene polymorphisms and the risk of developing migraine, although the association is still unclear.

• Clinical research suggests that the inhibition of the RAS by ACEIs and ARBs improves migraine.

• Currently, ACEIs and ARBs might be employed in migraineurs with comorbid arterial hypertension, but the evidence is still weak to support the current use of these drugs in migraine prophylaxis.

• Further research is needed to assess the tolerability of ACEIs and ARBs in normotensive subjects and to clarify whether their migraine-preventing action involves mechanisms other than those linked to the antihypertensive effect.

Notes