Learn how vascular restriction and dilation causes migraines and headaches. Discover how to identify the cause of your own migraines or headaches.

This article focuses on identifying the cause of migraines and headaches. If you want to see treatments, read this article describing 31 natural, science-backed remedies.

The Main Cause of Migraines and Headaches: Inflammation

It’s still controversial in the scientific arena whether a migraine is primarily a vascular (blood vessels) or a neurological dysfunction (dysfunction of neurons), but it’s likely that both have a significant role to play.

Genetics has been demonstrated to have a significant role in susceptibility to migraines and headaches (R). Go to SelfDecode to discover if your genetic makeup contributes to your risk.

Whether vascular or neurological, the source is likely brought on by inflammation.  Inflammation directly affects the vascular system and can damage neurons by causing ROS.

This post will focus on the role of “vascular instability” and how it’s affected in various ways. Vascular instability can be due to vasodilation (dilation of blood vessels and decrease of blood pressure) and vasoconstriction (constriction of blood vessels and increase of blood pressure).

I talk about various imbalances, but the source of these imbalances is usually a deranged immune system.  I don’t speak about the causes of inflammation in this post.

The neurological dysfunction aspect will have mitochondrial dysfunction as an additional underlying source.

I don’t discuss “spreading depression“, which is a significant mechanism in aura migraines (R).

Migraines vs Headaches

A chronic migraine is a disease which has headaches as the main symptom.

Isolated headaches are usually not caused by the same processes as migraines. Chronic migraines are usually caused by too much vasodilation.

Headaches can be caused by either too much vasodilation or vasoconstriction.

If someone has a tendency for either state, certain triggers can be tipping points which lead to a headache.

Migraines are more consistent and chronic, while vasoconstriction headaches are more sporadic and much more likely to be induced by environmental triggers such as stress or tyramines (both of which cause vasoconstriction).

Migraines, cluster headaches, and exercise headaches are generally caused by vasodilation. Tension headaches are caused by vasoconstriction.

The 3 Main Causes of Vascular Instability

These three causes are highly connected to one another and one cause can contribute to another. There are many interactions taking place.

Inflammation influences our endocrine and neurotransmitter levels and these can, in turn, modulate inflammation. Any hormone could lead to an increase or decrease of another hormone.

1) Inflammation.

Inflammation is a natural and healthy response to injury, but chronically high levels are problematic.

Specifically, a cytokine called IL-1b increases COX-2, which causes the trigeminal nerve, which mediates pain, to release calcitonin gene-related peptide (CGRP) (R).

CGRP release is perhaps the most significant cause of migraines.  During some migraine attacks, increased concentrations of CGRP can be found in both saliva and plasma drawn from the external jugular vein (R).

Furthermore, intravenous administration of alpha-CGRP is able to induce a headache in individuals susceptible to migraines (R).

Tumor necrosis factor alpha (TNF), another cytokine, can also increase the expression of the CGRP gene (R).  iNOS, which is induced by TNF and NF-kb (a transcription factor), also increases the expression of the CGRP gene (R).  MAPK also has a significant role in the inflammatory process that releases CGRP (R).  MAPK is caused by AGEs, which is caused by sugar, especially fructose.

iNOS produces nitric oxide, which causes vasodilation.  People with migraines with aura have an increased sensitivity to endothelial nitric oxide.  The result is more vessel dilation than is warranted when there is increased blood flow (R).

Further supporting the role of inflammation, studies have found people with migraines are more likely to have a variation of the gene that makes TNF-alpha.  These people have the “TNF-α -308G/A polymorphism”, which is associated with migraine risk (R).  This variation makes these people have a larger spike of TNF in response to an injury, infection or inflammatory agent (R).

This released CGRP then binds to and activates CGRP receptors located around meningeal vessels, causing vasodilation, mast cell degranulation and ‘leaky’ blood vessels (extravasation) (R).

Acute bouts of inflammation from injuries can, therefore, exacerbate these migraines.

In general, acute inflammation is characterized by marked vascular changes, including vasodilation, increased permeability and increased blood flow, which is induced by the actions of various inflammatory mediators (R).

Inflammation can also damage our mitochondria.  Mitochondrial dysfunction can amplify inflammation through ROS production and NF-κB activation (R).

Inflammation causes glutamate excitotoxicity and the cytokine IL-1b plays an important role in this, too (R).

Excitotoxicity causes a cascade of events such as an increase in free radicals and phospholipases, which break down the neuronal membrane, allowing harmful chemicals and ions to enter and ultimately degrading the cell’s mitochondria.

Inflammation also contributes to migraines because it causes changes in the trigeminal nerve, one of the main facial nerves that also houses a major pain pathway (R).

Migraine sufferers also are more likely than other people to have an incomplete network of arteries that supply blood to the brain.  This structural difference may cause frequent headaches or occur as a result of the headaches.

2) Endocrine Dysregulation

This is a dysfunction in the endocrine/hormonal system, sometimes of the HPA axis leading to unbalanced levels of:

This hormonal list is not comprehensive, but these are large players.

Since every one of these hormones plays a role in modulating the vascular system, it seems apparent to me that dysregulation of the endocrine system will result in either vasodilation or vasoconstriction.

When hormonal signaling is out of whack and too little or too much of one or more hormones is excreted at the wrong time you get excess vasodilation or vasoconstriction.

There also may be a role played by substance P and pain perception. Substance P is released along with glutamate, so if too much glutamate is released then there may be an increase in pain perception.  Substance P also causes neurogenic inflammation.

3) Neurotransmitter Dysregulation.

Glutamate (and aspartate), serotonin, acetylcholine, and GABA play the following role in vasodilation and vasoconstriction:

  • Glutamate causes vasodilation.
  • GABA causes vasodilation.
  • Serotonin is a vasoconstrictor – Serotonin deficiency causes vasodilation.
  • Acetylcholine is a vasoconstrictor. Acetylcholine deficiency causes vasodilation.

It was found that glutamate, a major neurotransmitter, is vasoactive in the cerebral circulation. Glutamate vasodilation is mediated by nitric oxide through NMDA receptors (R).

The levels of serotonin, a vasoconstrictor, seem to decrease during a migraine whereas an i.v. infusion of serotonin can abort a migraine. In fact, serotonin as well as ergotamine, dihydroergotamine, and other antimigraine agents invariably produce vasoconstriction in the external carotid circulation (R).

Acetylcholine is a vasoconstrictor (R).

According to one study, administration of GABA (1-100 micrograms) directly into the cerebral circulation produced dose-dependent increases in cerebral blood flow (R).

Substance P is released along with glutamate, so if too much glutamate is released then there may be an increase in pain perception.

Which Category Are You In?

Vasodilatory headaches

Your headaches may be caused by vasodilation if it occurs as result of:

  • Heat,
  • Sex and masturbation (both vasodilators)
  • Exercise (during or post)
  • An infection or sickness
  • An injury
  • Ingestion any food or chemical that they are sensitive to (gluten, casein, etc..)
  • Hypoglycemia
  • MSG
  • Hot flushes by perimenopausal women (increases vasodilation from estrogen)  Estrogen also fluctuates in pregnancy and  menarche
  • After menstruation –  estrogen levels peak ~11-13 days after

Exercise, infection, injury and food intolerances cause inflammation, which leads to vasodilation.

People will usually, but not always, have lower than average blood pressure because of vasodilation lowers blood pressure.

MSG or excess glutamine/glutamic acid consumption can worsen vasodilatory migraines because glutamate excess causes vasodilation.  The degree of harm caused by MSG is probably minimal.

Instead, glutamate excess is more likely caused by a host of other factors not related to dietary consumption of glutamates such as hypoglycemia caused by eating high glycemic index foods, hyperinsulinemia, fasting/skipping meals or really low carb dieting.

Also, low oxygen can cause glutamate excitotoxicity, such as when we are so stressed we forget to breathe, but more likely as a result of sleep apnea (if you get a headache in the morning check for sleep apnea).

Vasodilatory headaches are least responsive to nonsteroidal anti-inflammatory drugs (NSAIDs) like aspirin because while aspirin will block the pain to a certain extent and bring down inflammation, it is a vasodilator itself.  So in one way it makes it better (by decreasing inflammation) and in another it exacerbates the problem (by increasing vasodilation).  If your headaches don’t improve with aspirin, that’s another indicator that it’s caused by vasodilation.

NSAIDs have been shown not to work for vasodilatory headaches like cluster or exercise headaches because NSAIDs vasodilatory actions will only help for vasoconstrictive headaches.

Allergies and allergic reactions cause an inflammatory response which will trigger or make this headache worse.

Vasoconstriction headaches

People with vasoconstriction headaches will usually have higher blood pressure and experience episodes during times of stress. Tension headaches are a good example of this.

Stress and tyramines, for example, can trigger vasoconstriction.  Stress triggers vasoconstriction through cortisol, epinephrine, and norepinephrine.

Any stimulus that causes the body to release stress hormones such as fasting or skipping meals, emotional stress, cold, bright lights and loud noise can aggravate these headaches.

Tyramines, found in aged cheeses and other foods, displace norepinephrine from neuronal storage vesicles, which leads to vasoconstriction.  These headaches can come often but they aren’t as consistent as vasodilatory headaches.

These headaches are most responsive to NSAIDs like aspirin because aspirin is both a painkiller and vasodilator.  And indeed, the research demonstrates its effectiveness for tension headaches.

People with vasoconstricting headaches are more likely to have:

  • Stress
  • High blood pressure, which is caused by angiotensinII
  • High choline dosage
  • Serotonergic like SSRI’s and tryptophan or foods which contain high levels of tryptophan may increase serotonin levels and possibly exacerbate vasoconstriction headaches

Health Tools I Wish I Had When I Was Sick

At SelfHacked, it’s our goal to offer our readers all the tools possible to get optimally healthy. When I was struggling with chronic health issues I felt stuck because I didn’t have any tools to help me get better. I had to spend literally thousands of hours trying to read through studies on pubmed to figure out how the body worked and how to fix it.

That’s why I decided to create tools that will help others cut down the guesswork:

  • Lab Test Analyzer – a software tool that will analyze your labs and tell you what the optimal values are for each marker — as well as provide you with actionable tips and personalized health and lifestyle recommendations to help you get there.
  • SelfDecode – a software tool that will help you analyze your genetic data from companies such as 23andme and ancestry. You will learn how your health is being impacted by your genes, and how to use this knowledge to your advantage.
  • SelfHacked Secrets – an ebook where we examine and explain the biggest overlooked environmental factors that cause disease. This ebook is a great place to start your journey if you want to learn the essential steps to optimizing your health.
  • SelfHacked Elimination Diet course – a video course that will help you figure out which diet works best for you
  • Selfhacked Inflammation course – a video course on inflammation and how to bring it down
  • Biohacking insomnia – an ebook on how to get great sleep
  • Lectin Avoidance Cookbook – an e-cookbook for people with food sensitivities
  • BrainGauge – a device that detects subtle brain changes and allows you to test what’s working for you
  • SelfHacked VIP – an area where you can ask me (Joe) questions about health topics

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The information on this website has not been evaluated by the Food & Drug Administration or any other medical body. We do not aim to diagnose, treat, cure or prevent any illness or disease. Information is shared for educational purposes only. You must consult your doctor before acting on any content on this website, especially if you are pregnant, nursing, taking medication, or have a medical condition.


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