Indirect Regulation of Na⁺, K⁺-ATPase by Endocrine Hormones: Participation of Endocrine Hormones in the Sodium Theory for Migraine

Gordon R. Biringer, Ph.D¹

1. Professor of Biochemistry, LECOM Bradenton, 5000 Lakewood Ranch Blvd., Bradenton, FL 34211

OPEN ACCESS

PUBLISHED: 31 January 2025

CITATION: BIRINGER, Roger G.. Indirect Regulation of Na+, K+-ATPase by Endocrine Hormones: Participation of Endocrine Hormones in the Sodium Theory for Migraine. Medical Research Archives,  Available at: <https://esmed.org/MRA/mra/article/view/6232>.

COPYRIGHT: © 2025 European Society of Medicine. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ISSN 2375- 1924

Abstract

The European Migraine and Headache Alliance (https://www.emhalliance.org) estimates that migraines is one of the top ten leading causes of disability and affects 12-15% of the population, and is responsible for €27 billion of annual economic loss in terms of reduced productivity and work days lost. It is generally understood that migraine pathology is neurovascular. Vasodilation, neurogenic inflammation, and neuro-activation all play roles. However, more recent research has changed the emphasis from a primarily vascular cause to where the vascular component results from the neurological condition involving trigeminal nociceptive activation. Further, the data shows a decrease in migraines with increasing age for all groups. An earlier study showed that of the Norwegian population in the authors’ study, the authors speculated that the decrease in migraine in people with diabetes may be due to the fact that individuals with diabetes tend to have a lower incidence of migraine than non-diabetics, and individuals with diabetes still had a lower incidence of migraine than those individuals with type 2 diabetes. This review presents data regarding the relationship between insulin regulation of Na⁺, K⁺-ATPase and its potential role in the sodium theory of migraine. These results suggest that alteration in the homeostasis of endocrine hormones may lead to increased exacerbation of headache pain.

Keywords

• migraine
• Na⁺, K⁺-ATPase
• endocrine hormones
• insulin
• neurovascular

1. Introduction

The European Migraine and Headache Alliance (http://www.emhalliance.org) estimates that migraines is one of the top ten leading causes of disability, affects 12-15% of the population, and is responsible for €27 billion of annual economic loss in terms of reduced productivity and work days lost. It is generally understood that migraine pathology is neurovascular. Vasodilation, neurogenic inflammation, and neuro-activation all play roles. However, more recent research has changed the emphasis from a primarily vascular cause to where the vascular component results from the neurological condition involving trigeminal nociceptive activation.

2. Indirect Regulation of Na⁺, K⁺-ATPase by Endocrine Hormones

Human NKA is a dimer of heterotrimers consisting of α, β and γ subunits of which there are four known isoforms of the α subunit and 11 known isoforms of the β subunit (http://www.genetools.org). Human tissues typically have a mixture of various combinations of the subunit isoforms and the relative amounts of each are tissue dependent. Pumping rates depend on K⁺ and Na⁺ concentrations that, in turn, are specific for combinations of α and β isoforms and in some cases, auxiliary γ subunits where the α-subunit is responsible for pumping and ATPase activity, while the β-subunit stabilizes the pumping rate.

3. Angiotensin/aldosterone-based regulation

The relationship between elevated estrogen levels and migraine is complex. An early study showed a significant increase in migraine in women with elevated estrogen levels, while a later study showed that estrogen levels before menses were significantly higher in women with menstrual migraine compared to women without menstrual migraine. Further, the data regarding elevated angiotensin and aldosterone levels and their association with migraines is somewhat mixed; however, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers strongly inhibit the incidence of migraine.

4. Conclusion

This review presents data regarding the relationship between insulin regulation and increased NKA activity in the sodium theory for migraine. These results suggest that alteration in the homeostasis of endocrine hormones may lead to increased exacerbation of headache pain.

Conflict of Interest

The author has no conflicts of interest to declare.

Funding Statement

The author has no funding to declare.

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