Jo didn’t even realise that stress was triggering her migraines. Rather curiously she had a migraine at exactly the same time every two weeks. On further delving we identified that this was a couple of days before her step-children visited for their fortnightly stayover with their dad. The psychological stress of the build-up to this event would push her to her migraine tipping point.

Identifying this enabled her to put various stress coping measures in place.

Between 50% and 80% of migraine sufferers report stress as a migraine trigger. Numerous studies document this. (1) (2) (3) (4) (5) (6) (7)

1. Stress comes in many forms

Researchers differentiate between three major stress types:

  1. Daily – minor stresses of everyday life, mostly surmountable, but which can build up into long term chronic stress
  2. Chronic stress - which is the accumulation of daily stresses over a prolonged period
  3. Severe life stress – major traumatic events like long term abuse, divorce, war

Stress for most is a part of the fast pace of modern living. Work, finances, credit card debt,  mortgages, deadlines, keeping up with the Joneses, breakups, divorce, moving house, interpersonal conflicts, worries about a loved one who is ill are some of the many that we all know.

There are so many more stresses than ever before and even the modern smartphone constantly demanding to be answered can put much more subtle long enduring stress on the modern human.

The ability to light our homes and workspaces has meant that we tend to sleep later than people for whom night lighting is unavailable. This time is often then used to add more stresses to one’s life… staying up late, binge watching TV shows, playing shoot-em-up computer games as a few examples.

2. Chronic Stress can cause adrenal fatigue

When multiple stresses continue for a long period, and the person is unable to develop a coping mechanism, it becomes chronic stress.

This can lead to adrenal fatigue caused by what Dr James Wilson writes is "any type of stress that is chronic, prolonged or severe. Sufferers may be unaware of these stresses but their adrenals, being the glands of stress, have to compensate for each and every stress – physical, biochemical, hormonal, thermal, internal, external, emotional, mental, or toxic in origin, including overuse of drugs, alcohol and sugar".(8)

Wilson states that many such cases are triggered by:

  • motor vehicle accidents
  • severe injuries – especially head injuries and severe burns
  • deep emotional trauma such as divorce
  • extended periods of overwork without sufficient time for relaxation
  • poor and irregular eating habits
  • and chronic lack of sleep.

Certain groups tend to suffer from adrenal fatigue more frequently because of the constant stress they are under. Examples are caregivers, social workers, police, doctors, nurses, single moms, people working two jobs, lawyers, and the self-employed.(8) We can add to that shift workers, and flight attendants and pilots for whom the stress can be compounded by the crossing of multiple time zones.

Other stresses are continuous loud noise, driving, and overwhelm of "too many things to do".

Another major stressor is prolonged periods of domestic violence and abuse. Long term living with high levels of cortisol and adrenaline in the body resulting from the fear, mental and physical damage can lower the migraine threshold contributing to migraine.

3. Stress releases a cascade of chemicals for fight or flight

There are several ways that stress contributes to migraine. They involve the release of chemicals and the downstream effects.

When we experience a threat the body reacts with a fight or flight response.

For example, imagine that while strolling about the plains of Africa you encounter a lioness going about her food gathering routines. The brain instantly signals the body, through the central nervous system, to prepare its defences for an immediate response.

Your two adrenal glands (one sitting above each kidney) are the body’s stress centres, and they pump the stress hormone adrenaline (also called epinephrine) into the bloodstream. This triggers the production of another hormone, cortisol.

The hormones estrogen and testosterone are also released, as are the neurotransmitters serotonin and dopamine.

4. DHEA is released to balance the negative effects of cortisol - overstimulation

Stress also induces the adrenal glands to express dehydroepiandrosterone  (DHEA)  which counteracts the effects of cortisol. DHEA protects neurons from becoming overstimulated by amino acids that try to excite it into action, which can lead to neurotoxicity.(9) Neurotoxicity is where too many signals hit the brain at once and the brain cells get overloaded. Neurotoxicity can lead to migraine.

As you get older your DHEA levels reduce to the point that when you are 70 they are about 20% to 30% lower than those of people in their twenties, so the older you get the less able is DHEA able to protect you from some of the negative effects of cortisol and excitatory amino acids.(10) (DHEA is needed to produce sex hormones androgens and estrogens. Androgens are responsible for male characteristics and estrogens are key players in the female reproductive system.)

But if your body becomes physically fatigued from chronic stress it may produce less DHEA. It becomes a vicious cycle.

If the adrenal glands are fatigued there is less DHEA released. With chronic stress the adrenals continue to pump out cortisol and adrenaline while the levels of DHEA may struggle to counteract the cortisol.

It is interesting to note that in a study by Universidade Federal do Rio Grande do Sul scientists they found that DHEA in vitro increased glutamate release by 57% in murine studies. The good side of this is that it improved memory scores.(11) However we also know that excess glutamate in the migraine-sensitive person can lead to a migraine!

5. Stress and cortisol suppress the immune system

Stress and cortisol suppress the immune system. It does this to allow the body’s resource to be 'all hands on deck' to carry out the fight or flight response. If this is temporary the body and brain work towards re-establishing stability (homeostasis), and the adrenaline and cortisol dissipate. But when stress is chronic cortisol and adrenaline remain on 'high alert' and keep all the downstream chemicals on 'stand-by'.

The body tries to maintain adrenal stability via the hypothalamic-pituitary-adrenal (HPA) axis but chronic stress can upset this balance.

6. Just HOW does stress contribute to a migraine?

One of the most important effects of stress is that it depletes magnesium in the body.

Chronic stress (long term, enduring stress) can lead to magnesium deficiency symptoms. The greater (and longer) the stress, the greater the magnesium depletion. The lower one’s initial levels of total magnesium, the greater the negative effects of stress on your magnesium stores.(12)

Magnesium plays a major role in migraine protection by guarding the brain’s neurons from excess glutamate and calcium. When in excess, these minerals can cause neuronal overexcitation, cell death, seizures and migraine in those whose constitution makes them sensitive...like migraineurs.

Excess glutamate can induce migraine aura as too many signals jam up the synapses between neurons.

Magnesium usually sits inside cells. Depletion of magnesium allows glutamate to excite the NMDA receptors in the neurons and this causes the magnesium blocking the neuron to stop ‘guarding’ the NMDA receptor, allowing calcium into the neurons. This in turn leads to the release of CGRP. CGRP is the major peptide identified in migraine pain, and is what major drug companies are now trying to focus on suppressing with new drugs. Nature already has provided us with a CGRP suppressor in the form of the ginger plant.

7. How do chemicals released by stress deplete magnesium?

Stress hormone cortisol causes a depletion of magnesium.

The stress hormones adrenaline and cortisol require large amounts of energy. Much of this energy comes from ATP in the mitochondria (the cells’ power stations) and requires a lot of magnesium. It also requires a great deal of coenzyme Q10 to stoke the furnaces of the mitochondria.

We all know stories of someone who when primed with adrenaline has carried out almost superhuman feats. That energy has to come from somewhere, and magnesium and coenzyme Q10 are both important factors.

Dr Leo Galland writes that combined with this adrenaline blocks the uptake of magnesium into the cells, as well as increasing blood pressure.(13) Dr Carolyn Dean also documents this in her extensive writings on magnesium.(14)

The lower your levels of total magnesium the higher your level of adrenaline when experiencing stress. Higher levels of adrenaline then causes a greater loss of magnesium from cells, creating a vicious cycle.(12)

Magnesium deficiency produces a range of clinical effects jointly called tetany syndrome (TS). These  symptoms include muscle spasms, twitching, cramps, hyperarousal, hyperventilation and asthenia. Some of the more serious neurologic consequences of magnesium deficiency are headaches, migraine attacks, transient ischemic attacks, sensorineural hearing loss and convulsions.(12)

Stress, both mental and physical, causes magnesium to be drawn out of the cells in the tissues, muscle and bones and into the blood stream. This causes serum magnesium to increase. From there, what is not used in the mitochondria and other parts of the body, passes through the kidneys.

The kidney sensing its high levels will excrete what it deems as excess magnesium out through the urine.(12)

This eventually depletes the body’s stores of magnesium. The takeaway from this is that serum magnesium may be high not because you have lots of magnesium in the body, but because the body draws from its magnesium reserves to put it to work where it is immediately needed. So a blood test showing that you have high serum magnesium does not necessarily mean that you have high or ‘normal’ levels of magnesium. It may mean that your body has had magnesium drawn from the tissues and into the blood to meet immediate demands for it.

People exposed to chronic stress have been found to have significant decreases in plasma ionized magnesium 2+, total magnesium and ionized calcium 2+.(12)

8. Depleted magnesium means less serotonin

With depleted magnesium the brain releases less serotonin  which is one of the body’s natural "feel-good" chemicals. Increasing serotonin is one the how the triptan family of migraine drugs work. Low serotonin is identified in a 2007 paper by McGill University researcher Dr Hamel as a frequently occurring factor in migraine suggesting "that migraine is a consequence of a central neurochemical imbalance that involves a low serotonergic (serotonin) disposition".(15)

Serotonin (also known as 5-hydroxytryptamine - 5-HT) has been implicated in migraine pathophysiology for the past 50 years. A low central 5-HT disposition associated with an increase in 5-HT release during attack is the most convincing change of 5-HT metabolism implicated in migraine.(16)

Reduced serotonin means that those who are sensitive to migraine have another dent in their defences as serotonin depletes.

Panjab University researchers record that "varying levels of ovarian hormones especially estrogen influence serotonin neurotransmission system and CGRP levels making women more predisposed to migraine attacks."(17)

9. Stress causes Oxidative Stress

A further major link between stress and migraine is that stress causes oxidative stress.

Oxidative stress occurs when you do not have enough antioxidants to clear out oxidants.

10. Oxidants are like oxygen rust

Oxidants are the byproducts of the cells using up oxygen. For example when iron is exposed to oxygen and water, an oxidant byproduct is rust.

So when your mitochondria (the cells' furnaces) burn up oxygen going about their business of fuelling the body and providing it with energy they produce byproducts. These are called reactive oxygen species (ROS). We can consider these to be "cellular rust".

If you ever see the word oxidise or oxidationjust think oxygen rust. Think of a consequence of this as being corrosion in the body.

11. Antioxidants combat oxidants

We are all familiar with the term antioxidants and know that they are good for us. Antioxidants usually moderate oxidants and clear them out. Common antioxidants include vitamin A, C, E, beta-carotene, lutein, lycopene, selenium, and we all know that fresh fruit and vegetables are packed with them. Powerful antioxidants also include ginger, curcumin and astaxanthin. Consider them as 'anti-cellular rust' agents.

Dr Stefania Schiavone et al from the University of Geneva wrote in 2013 study that people exposed to severe life stress (SLS), as opposed to trivial everyday stress, suffered oxidative stress in the central nervous system (CNS) resulting in many downstream pathophysiological outcomes.(18)

In other words chronic stress decreases both free and total magnesium, as described above, while the excessive accumulation of reactive oxygen species (ROS) simultaneously increases oxidative stress.(19)

12. Why does stress release ROS?

When we encounter a flight or fight situation our body gets a blast of adrenaline, cortisol and other chemicals to prepare it for immediate self-survival. The brain instantaneously prioritises protecting the body and rallies all its available resources to fight the attacker or flee from it. In the short term this sudden release of ROS involves a surge of excitatory neurotransmitters.

13. ROS induces glutamate release

Included in this mix is a surge of glutamate.(18) Being a neurotransmitter, lots of glutamate is needed to pass messages among the brain cells quickly while dealing with the threat.

Once the threat has gone, been beaten, fled or been fled from, the body re-establishes equilibrium.

However when the stress is ongoing and chronic these chemicals stay in the bloodstream, body and brain in abnormally high, and often imbalanced quantities. Excessive glutamate is shown to be a major factor in many migraines in those who are migraine-sensitive.

Russian and French researchers found that when ROS accumulated and antioxidants are in insufficient supply  a "massive, abrupt, and detrimental change in cellular functions occurs (in brain cells), a phenomenon that they call metabolic collapse (MC).(20)

The consequences of MC resemble cortical spreading depression (CSD), a wave of neuronal depolarization that occurs in migraine, brain trauma, and stroke. They suggest that ROS accumulation might also be the primary trigger of CSD, and noted that it was prevented with the antioxidant tempol.

14. Depleted Magnesium escalates the inflammatory cascade

Doctors Weglicki and Phillips et al of George Washington University identify that magnesium deficiency escalates the inflammatory cascade of chemicals. These are things like substance P, interleukins IL-1 and IL-6, tumor necrosis factor alpha (TNF-α), chemokines and cytokines. Inflammation can be worse especially when combined with excess calcium.(21) We know that inflammation causes an immune system response which can lead to migraines.

15. ROS and oxidants escalate the inflammatory cascade

Wikipedia tells us that research indicates close associations between ROS and chronic inflammation. ROS induces chronic inflammation by the induction of chemicals with wonderful names like COX-2, inflammatory cytokines (TNFα, interleukin 1 (IL-1), IL-6), chemokines (IL-8, CXCR4) and pro-inflammatory transcription factors (NF-κB).(22)

University of Medicine Berlin scientists in 2011 identified a COX-2 dependent pathway of cytokine induced CGRP release in trigeminal ganglia neurons that is not affected by 5-HT1B/D receptor activation.

Activation of neuronal and glial cells in the trigeminal ganglion by IL-1β leads to increased expression of COX-2 in these cells.

Newly synthesized Prostaglandin E2 (by COX-2) in turn activates trigeminal neurons to release CGRP.

These findings support a glia-neuron interaction in the trigeminal ganglion and demonstrate a sequential link between COX-2 and CGRP. The results could help to explain the mechanism of action of COX-2 inhibitors in migraine.(23)

As you can see, stress has many ways that it can affect migraines. Lower your stress levels, and finding coping mechanisms will raise your migraine threshold and allow your body to withstand more assaults that contribute to migraine.

What can we do ? Reduce stress now and raise your migraine threshold

There are many, many strategies for reducing stress, and raising your body’s migraine threshold.

Research shows that relaxation therapies, biofeedback and stress management therapies are effective in migraine treatment.(1) We look at these in more detail here:

> 23 ways to reduce stress and raise your migraine threshold


By Kevin the Migraine Researcher
Migraine Escape, Innovative Herbal Products


References

  1. Stress and Migraine. Radat, F. 5, Paris : s.n., May 2013, Revue Neurologique, Vol. 169, pp. 406-412.
  2. Stress as a trigger for headaches: relationship between exposure and sensitivity. Martin, P R, Lae, L and Reece, J. 4, Dec 2007, Anxiety, Stress, Coping, Vol. 20, pp. 393-407. Department of Psychological Medicine, Monash University, Monash Medical Centre, Clayton, Australia.
  3. Stress and migraine interaction. Sauro, K M and Becker, W J. [ed.] Wiley Online Library. 9, Oct 2009, Headache, Vol. 49, pp. 1378-86. University of Calgary and Alberta Health Services, Calgary, AB, Canada.
  4. Post-traumatic stress disorder in episodic and chronic migraine. Peterlin, B L, et al. 4, s.l. : Wiley Online Library, Apr 2008, Headache, Vol. 48, pp. 517-22. Drexel University College of Medicine-Neurology, Philadelphia, PA 19102, USA..
  5. Migraine: Maladaptive Brain Responses to Stress. Nasim , Maleki, Becerra, Lino and Borsook, David. (Supp 2), Oct 2012, Headache, Vol. 52, pp. 102-106. Author Info: Center for Pain and the Brain, Children’s Hospital Boston, Harvard Medical School.
  6. Stress and chronic headache. d'Amico, D, et al. s.l. : Springer-Verlag, 2000, Journal of Headache Pain, Vol. 1, pp. S49–S52. C. Besta National Neurological Institute, Milan, Italy.
  7. The association between stress and headache: A longitudinal population-based study. Schramm, S H, et al. 10, s.l. : Sage Journals, Sep 2015 , Cephalalgia, Vol. 35, pp. 853-63.
  8. Clinical perspective on stress, cortisol and adrenal fatigue. Wilson , James L. 2, s.l. : Elsevier Science Direct, May 2014, Advances in Integrative Medicine, Vol. 1, pp. 93–96.
  9. Dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEAS) protect hippocampal neurons against excitatory amino acid-induced neurotoxicity. Kimonides, V G, et al. 4, s.l. : National Academy of Sciences of the USA, 1998, Proceedings of the National Academy of Sciences of the USA, Vol. 95, pp. 1852-1857. Author info: Department of Anatomy and ‡Medical Research Council Cambridge Centre for Brain Repair, University of Cambridge, United Kingdom.
  10. Study of the stress response: role of anxiety, cortisol and DHEAs. Boudarene, M, Legros, J J and Timsit-Berthier, m. 2, Mar-Apr 2002, Encephale, Vol. 28, pp. 139-46. Author info: Bat G, N 266, Cité Djurdjura, Ville Nouvelle, Tizi Ouzou 15010, Algérie.
  11. Dehydroepiandrosterone increases synaptosomal glutamate release and improves the performance in inhibitory avoidance task. LHullier, F L, et al. 3, Mar 2004, Pharmacology, biology and behaviour, Vol. 77, pp. 601-6. Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Pôrto Alegre, RS, Brazil.
  12. Magnesium, stress and neuropsychiatric disorders. Galland, L. (2-4), 1991-1992, Magnesium Trace Elements, Vol. 10, pp. 287-301.
  13. Galland, Leo and Galland, Jonathan. The Allergy Solution; the Surprising, Hidden Truth about why you are Sick and How to get Well. Carlsbad : Hay House, 2016.
  14. Dean, Carolyn. The Magnesium Miracle. New York : Ballantine Books, Random House, 2014. p. 178. 978-0-345-49458-0.
  15. Serotonin and migraine: biology and clinical implications. Hamel, E. 11, Montreal : Sage Journals, Nov 2007, Cephalagia, Vol. 27, pp. 1293-300. Author info: Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montréal, Québec, Canada.
  16. Serotonin and migraine: a reconsideration of the central theory. Panconessi, Alessandro. s.l. : Springer-Verlag, 26 June 2008, Journal of Headache Pain, Vol. 9, pp. 267–276.
  17. Serotonin and CGRP in Migraine. Aggarwal, Milan , Puri, Veena and Puri, Sanjeev . 2, s.l. : Karger, Apr 2012, Annals of Neurosciences, Vol. 19, pp. 88–94. Author info: Panjab University, Chandigarh, India.
  18. Severe Life Stress and Oxidative Stress in the Brain: From Animal Models to Human Pathology. Schiavone, Stefania , et al. 12, s.l. : Mary Ann Liebert, Inc, 2013, Antioxidants and Redox Signalling, Vol. 18. Author info: Dr. Stefania Schiavone, Department of Pathology and Immunology, University of Geneva, Switzerland.
  19. Alterations in magnesium and oxidative status during chronic emotional stress. Cernak, I, et al. (1), Mar 2000, Magnesium Research, Vol. 13, pp. 29-36. PMID: 10761188; Author info: Military Medical Academy, Belgrade.
  20. Reactive oxygen species initiate a metabolic collapse in hippocampal slices: potential trigger of cortical spreading depression. Malkov, A, et al. 9, s.l. : Sage Journals, Sept 2014, Journal of Cerebral Bloodflow Metabolism, Vol. 34, pp. 1540-9. Author info: Russian Academy of Sciences, Pushchino, Russia; Institut de Neurosciences des Systèmes, Marseille, France; Kazan Federal University, Russia; Insitute of Biophysics and Cell Engineering, Minsk, Belarus..
  21. Magnesium-deficiency elevates circulating levels of inflammatory cytokines and endothelin. Weglicki, William B, et al. 2, s.l. : Kluwer Academic Publishers-Springer Link , March 1992, Molecular and Cellular Biochemistry, Vol. 110, pp. 169–173. Author info: Departments of Medicine and Physiology, The George Washington University Medical Center, USA.
  22. Upsides and Downsides of Reactive Oxygen Species for Cancer: The Roles of Reactive Oxygen Species in Tumorigenesis, Prevention, and Therapy. Gupta, S C, et al. 11, s.l. : Mary Ann Liebert, Inc, 1 Jun 2012, Antioxidants and Redox Signaling, Vol. 16, pp. 1295-322.
  23. IL-1β Stimulates COX-2 Dependent PGE2 Synthesis and CGRP Release in Rat Trigeminal Ganglia Cells. Neeb, Lars, et al. [ed.] Stefan Bereswil. (3), s.l. : Plos One, 4 March 2011, Vol. 6. Author info: Department of Neurology and Experimental Neurology, Charite Universitatsmedizin Berlin, Germany, Department of Neurology, Universitatsklinikum Tubingen, Germany.