Potential Role of Arterial Hypertension in Migraine Pathogenesis

The question of whether migraine is exclusively neurogenic in nature or the product of vascular dysfunction has yet to be fully elucidated due to the paucity in data on this topic. Given the complex pathophysiology of migraine and comorbid phenomena, it seems plausible that a systemic catalyst could be implicated, and several studies have shown associations between hypertension and the development of migraine in clinical settings.¹ The propensity for migraine to lead to hypertension sheds new light on the links between the nervous and vascular systems.

Headaches that are attributed to hypertension are the result of disordered hemostasis that causes secondary headache. International guidelines state that for a headache to be attributed to hypertension, systolic blood pressure (BP) should rise quickly to ≥180 mmHg or diastolic BP should rise to ≥120 mmHg, and the headache resolves with BP normalization. The characteristics of these headaches are often described as bilateral and pulsating. There is also no convincing relationship between BP fluctuations over a 24-hour period and the absence or presence of headache in ambulatory BP monitoring of patients with mild and moderate hypertension.²

Most studies point to a positive association between migraine and arterial hypertension, and studies finding contradictory results may be partially explained by the difference in the relationship between systolic and diastolic values and incidence of migraine.³ Bigal and colleagues found that compared with patients without migraine, patients with migraine had a 1.4-fold increased risk for hypertension.⁴ Longitudinal studies have had similar findings of this association, including other demographic predictors such as sex, age, body mass index, and alcohol consumption.^5,6

Mechanisms of Migraine and Hypertension
Many studies support the hypothesis that patients with migraine have an increased risk of developing arterial hypertension, based on common mechanisms shared by migraine and hypertension, such as endothelial dysfunction, deficiency of autonomic cardiovascular regulation, and renin angiotensin system involvement. Arterial sensitivity to nitrous oxide, an important molecule in regulation of cerebral cranial blood flow, is believed to be a trigger for migraine attack.⁷ A simpler, mechanistic explanation is based on the activation of the sympathetic nervous system in patients with migraine immediately prior to attacks. With rising concentrations of catecholamines, particularly norepinephrine, the sympathetic activation causes platelet aggregation and vasoconstriction. Babayan and colleagues found that patients with migraine showed higher values of vasomotor reactivity independent of their hypertension status; the subgroup of patients with both migraine and hypertension showed arterial baroreflex reduction and orthostatic hypertension, leading the authors to conclude that the reduction in arterial baroreflex contributes to the development of arterial hypertension in migraine.⁸ Antihypertensive agents, traditionally β-blockers and angiotensin-converting-enzyme inhibitors and angiotensin II receptor blocks, may have a preventive effect on migraine.

Ongoing Research on Links Between Migraine and Hypertension

Researchers have focused on findings around the driving force of disordered cerebral autoregulation as the reason for the headaches experienced by patients when BP becomes uncontrolled. The sensation of pain is thought to originate from proximal portions of large intracerebral blood vessels that are innervated by neurons projecting signals to the trigeminal nucleus caudalis in the medulla, which communicates with the hypothalamus and cortical structures.^9,10 This may explain the incidences of acute headache that accompany sudden rises in BP, although this does not provide an explanation for headache due to chronic, sustained elevations in BP.

Research investigators suggest that the autonomic nervous system may play a role in the pathogenesis of migraine, but the findings are mixed. A definitive association between the autonomic nervous system and migraine is difficult to confirm because of the sympathetic hypoactivation and hyperactivation as well as parasympathetic dysfunction that have been observed at baseline in patients with migraine.^11,12 More research is needed to help determine the association between migraine and arterial hypertension above and beyond that of endothelial dysfunction.

References

1. Arca KN, Halker Singh RB. Headache Classification Committee of the International Headache Society (IHS) (2014) The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia 2014;33(9):629–808.

2. Arca KN, Halker Singh RB. The hypertensive headache: a review. Curr Pain Headache Rep. 2019;23(5):30.

3. Finocchi C, Sassos D. Headache and arterial hypertension. Neurol Sci. 2019;38(suppl 1):S67-S72. doi: 10.1007/s10072-017-2893-x

4. Bigal ME, Kurth T, Santanello N. Migraine and cardiovascular disease: a population-based study. Neurology. 2010; 74:628-635.

5. Courand PY, Serraille M, Girerd N, et al. The paradoxical significance of headache in hypertension. Am J Hypert. 2016; 29:1110-1116.

6. Entonen AH, Suominen SB, Korkeila K, et al. Migraine predicts hypertension—a cohort study of the Finnish working-age population. Eur J Pub Health. 2013; 24(2):244-248.

7. Olesen J. The role of nitric oxide (NO) in migraine, tension-type headache and cluster headache. Pharmacol Ther. 2008; 20:157-171.

8. Babayan L, Oleg V, Mamontov OV, Amelin AV, Bogachev M, Kamshilin AA. Arterial hypertension in migraine: role of familial history and cardiovascular phenotype. Autonom Neurosci Basic Clin. 2017; 203:103-107.

9. Cutrer FM. Pathophysiology of migraine. Semin Neurol. 2010;30(2):120-130.

10. Arca KN, Halker Singh RB. SUNCT and SUNA: an update and review. Curr Pain Headache Rep. 2018;22(8):56.

11. Matei D, Constantinescu V, Corciova C, Ignat B, Matei R, Popescu CD. Autonomic impairment in patients with migraine. Eur Rev Med Pharmacol Sci. 2015;19(20):3922-3927.

12. Miglist MG. Migraine and autonomic dysfunction: which is the horse and which is the jockey? Curr Pain Headache Rep. 2018;22(3):19.