electrolyte

Hydration, Thirst, and Drinking Water

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drinking water, hydration

Most of us equate the expression “hydrate extra” with drinking more water but – unfortunately – this is incorrect. In any online dictionary “to hydrate” means to create “…a substance that is formed when water combines with another substance…” In other words, water alone is not a hydrating fluid but it must be combined with something to become one. We do not have water in our body on its own; we have a substance we call electrolyte. I wrote substantially on the topic of hydration, mixing water with minerals, as part of the protocol that prevents migraines. However, a new problem has surfaced: when to drink water? Several articles have recently published water drinking instructions on the internet. Most of these articles consider it bad practice to drink water when one is not thirsty and recommend drinking water only when thirsty. There are several serious flaws with this argument.

Sweat

The first flaw is that most research is aimed at athletes, but athletes are not representative of the majority of the population. Furthermore, athletes should not be drinking “water” to hydrate. Drinking water cannot be absorbed by cells without adequate sodium to hold onto it. When athletes sweat, the content of sweat is not water but electrolyte. Many sports drinks aim at re-hydrating athletes but their problem is their sugar or sugar substitute content, defeating the purpose — see how much sports drink one needs to drink to make up the content of sweat for an athlete. Then add up the sugar in a typical sports drink: 1 teaspoon of sugar is 4 grams of carbs. An average serving of a typical sports drink provides between 14 grams to 54 grams of carbs, all sugar, which converts to 3.5 to 13.5 teaspoons of sugar per serving. Drinking sugar substitutes is even worse because sugar substitutes fool the body like it is receiving glucose so insulin spikes but there is no glucose. This creates insulin overflow in the blood causing you to become hungry! Sugar substitutes may lead to obesity and metabolic syndrome. Drinking sports drinks with sugar substitutes actually reduces muscle energy.

Moreover, anything that converts to glucose in the body removes both water and sodium from the cells1 so drinking/eating sugar with sodium (salt is the form in which sodium is available to us) and water is worse than not drinking anything at all. Many athletes have smartened up and drink pickle brine rather than water. Pickle brine is great, assuming the brine is of salt and water and not vinegar. Vinegar is fermented ethanol (alcohol). Thus, drinking vinegar-processed pickles will dehydrate further. Look for pickles made with salt rather than vinegar.

Best Hydrating Fluid

Whole milk is an ideal hydrating fluid because it has a perfect electrolyte balance in sodium, potassium, water, blood sugar (lactose), calcium, phosphorus, magnesium, and protein. Whole milk is THE perfect electrolyte. Some athletes drink water and take salt pills (also called electrolyte pills). That is also a great option, particularly since they are easy to carry around and take when needed.

The second flaw in the argument of “drink water when thirsty” is that many people feel thirst after eating sugar when it is the least advisable to drink water. Since about half of sugar converts to glucose, and glucose pulls water and sodium out of the cells1, if one is thirsty after eating sugar and drinks water, the metabolic process will remove more water from the cells. This can cause edema. Although most articles today blame salt for causing edema, the opposite is true.

While sodium retains water inside the cell, glucose removes water and sodium from the cell and forces the water to be retained in extracellular space2. Eating salt when one has edema reduces edema by the sodium bringing water back into the cell. This was easily demonstrated by a previous article showing how this works.

The problem with most studies that blame salt on retaining water is that no studies have ever controlled for both salt and sugar at the same time in the same experiment. All studies I could find only looked at the effects of salt on the body regardless of the amount of sugar, water, or protein the subjects had consumed before the experiment. Since the body can easily be tipped out of balance and is never in a vacuum for a pristine controlled experiment, one cannot say with certainty that one element makes a particular change without looking at what else is affecting the body. No such studies exist except in my migraine group where we control for all variables. We found that being thirsty often means the person does not have enough salt to keep water where it belongs3. A migraineur should never drink water when she is thirsty, particularly not if carbohydrates were consumed.

The final problem with only drinking water when thirsty is the population of people who have diabetes 2; they are always thirsty. Being thirsty can be a sign of diabetes mellitus and not the need for more water.

Should You Wait Until You Are Thirsty Before You Drink?

Absolutely not, and for sure drinking water alone will not get you hydrated. How much water you should drink is a question I will address in another article. Drinking the minimum 8 glasses of water is a myth; people vary in size, age, and activity, implying that each person needs a different amount of water. Many online water calculators go into detail of weight, climate, activity, altitude, your health, pregnancy, nursing, etc. For each person the amount of water and thus hydration needed (not just water) will differ and for that hydration level you need to make sure you drink adequate amounts of water as part of your hydration protocol.

Sources

  1. Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J. Harrison’s Manual of Medicine 18th Edition. New York: McGraw Hill Medical; 2013.
  2. Millar T. Biochemistry Explained: A Practical Guide to Learning Biochemistry. Vol reprint edition: CRC Press; 2002.
  3. Stanton, Angela A. Fighting The Migraine Epidemic: A Complete Guide: How To Treat & Prevent Migraines Without Medicine

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Happy Ending to Migraines: The Benefits of Milk

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Raw milk migraine

Migraines and Electrolytes

In late June of 2015, I received a PM (personal message) on Facebook from a husband of a migraineur. The husband introduced himself and explained that his wife “suffered with migraines for 15 years (Oct. 2000) after hitting her head under a bathroom cabinet.” She had been through all kinds of typical migraine treatments – just about everything under the sun possible to try, including a neuronal stimulator placed in via surgery – but nothing has worked. As he was sitting in the hospital waiting for some results, he found me on Facebook and asked for help.

I have a standard questionnaire that I ask all migraineurs to fill and send the answers to me via PM so I can see what may be wrong. The first thing that hit me was that she was drinking 256 oz (32 glasses) water a day when the calculator suggested that her petite figure needed only 66 oz (just over 8 glasses) so something was terribly wrong. She also took a ton of medications, though the list he sent was already greatly reduced. Even with these medications, she suffered debilitating migraines every day.

The migraineur was Kristen Cassimatis. Her recovery was covered recently by a local television station on their news. You can watch it here: Raw milk helping woman relieve migraine pain.

What Do Electrolytes, Whole Milk, and Migraines Have in Common?

A lot actually. The very first article I published at Hormones Matter was on the importance of proper hydration to the body. Hydration is not water but a mix of electrolyte minerals with water, of which sodium and potassium (in proper balance) are the most important. An article I wrote somewhat later describes what excessive thirst means for the body and that sugar is really bad for you. Thus, if you look through some of the articles I published, you can see that a meal that is hydrating, contains no added sugar, has protein and some minimal carbs, electrolytes, and fat. Fat is good for you. I have also published several academic journal articles on the cause and treatment of migraine, based on statistical findings in the migraine group on Facebook.

I have not yet discussed fat and cholesterol in great detail but an article shall come about that in the near future. For now, since whole milk is full of saturated fat and cholesterol, I just want to mention a few important findings. It is important to note that over 70% of our brain is fat and 25% of all cholesterol in our body is found in our brain (1) in what is called the white matter where voltage transmitting axons are coated with cholesterol (myelinated). Thus, cholesterol and fat are important for us.

While there is a huge controversy over the benefit versus harm of saturated fats and cholesterol, more studies now show that saturated fats and higher levels of cholesterol are actually better for us, particularly for women. In fact, saturated fat is not associated with heart disease as suggested by many studies.

To add insult to injury, cholesterol is not actually made from fat but from acetoacetyl-CoA (2) by a 19-step process in the liver. We can choose to eat cholesterol but if we don’t eat enough, the liver has to make cholesterol. When we don’t eat cholesterol, the liver makes less cholesterol than each person’s optimal level (2). The only bad cholesterol our liver makes are triglycerides that do clog up arteries but they are made of sugar and under special circumstances. Thus, regardless in what stage studies are at now, something that every single cell is made of in our body – the membrane of each human cell is made of lipid bilayer – cannot possibly be bad for us: we are made of the stuff.

As in the story above, someone who feels the urge to drink a lot of water is usually not getting enough or the right balance of electrolytes. Moreover, the act of drinking too much water is harmful since it dilutes electrolytes. Drinking whole milk, which is full of electrolytes, on the other hand, is good for us migraineurs and others alike. Few people realize that milk is a great source of electrolytes, protein, and good cholesterol. Most of us were told from early on in our lives that milk is for cows and not people; milk is bad for us; it has puss in it; it causes puss; it makes one phlegm up; it makes us fat; it has too much fat; etc. We have been told not to drink milk, and as a result, many folks are having difficulty managing electrolyte and cholesterol balance.

I think that milk is a perfect food, assuming of course, that it is organic, whole milk, not treated with hormones and antibiotics, as in the story above. Raw milk is not legal everywhere so while drinking safe raw milk is healthier, it may not be available to everyone. Reduced fat milk does not have the benefits of whole milk and also contains added sugar and proteins that are not all that great for you. In fact, if you have no time to eat a meal, be it breakfast, lunch, or dinner, a glass of whole milk is an ideal replacement.

So, as Kristin recovered from her migraines and is also preparing to have her brain stimulator surgically removed, she joined the thousands of migraineurs who have joined our migraine community on Facebook. Enjoy Kristen’s story and join the several thousands who have been able to stop all their medicines and remained migraine free.

Sources

  1. Perlmutter D & Loberg K (2014) Grain Brain: The Surprising Truth About Wheat, Carbs, and Sugar – Your Brain’s Silent Killers (Hodder & Stoughton).
  2. Dr. Kendrick M (2007) The Great Cholesterol Con; The truth about what really causes heart disease and how to avoid it (John Blake Publishing, London, England) p 270.

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Triptans ± SSRIs ± Migraines ± Depression: Flip a Coin!

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Angela Stanton, PhD

Migraines and depression are understood to be neurological diseases though many consider them to be mental illnesses [1, 2]. Recent research sheds light on both conditions and shows us how much they have in common. Both migraines and depression can be stopped by voltage applied to the brain. In the case of depression, voltage has only been applied via open-brain surgical procedures as deep brain stimulation of the specific brain region, shown in the scanner as dark region [3-6]. For migraines the stimulation has been tried both outside of the brain [7, 8] and internally via deep brain electrical stimulation [9]. The cause inn both migraine and depression is seen in scanners [1, 10] as cortically depressed areas. These are dormant regions that have no observable electrical activity. When electrical stimulation is applied to a dormant brain region, it regains its function. Crucially for migraines, it has been demonstrated that a dormant area be shocked by a wave of electricity generated by the brain itself, called cortical spreading depression, energizing the dormant area to be able to create action potential again [11-14]. This is quite similar to a cardiac arrest patient receiving an electrical shock to the heart which restarts electrical activity. The difference is that in the case of the heart the electricity is applied externally by others, whereas in the case of the brain the electric shock is applied by the brain itself by using its functioning brain regions to energize nonperforming regions. Because neurons communicate to each other via neurotransmitters and are connected to each other, neurons that do not manufacture neurotransmitters and do not participate in communication exchange cannot hide. The healthy, energized regions send a wave of energy within the brain. However, this wave reaches the meninges where all pain sensory neurons are located [14] and hence migraine pain.

Similarly to how a cardiac arrest does not always get the heart to continue beating again, the electric shock of the spreading cortical depression may not awaken the dormant regions either. Energy for proper functioning of either the heart or the brain – or indeed for any living tissue – cannot be created from nothing. To continue to generate voltage after the initial shock, the proper minerals have to be available. One can only drive a car on fumes for so long. Interestingly we understand this very well when it comes to our cars but we tend to forget it when it comes to our body. Our body uses energy it receives from what we eat and drink. The energy is carried to the cells by electrolytes. Electrolytes are water mixed with vital nutrients. Electrolytes take up 55%-70% of our body per gender and age with salt about 9 grams per liter. Those brain regions that lack important nutrients will not function.

We now understand that brain regions that are starved of energy and that are not able to generate action potential cause abnormal synaptic transmissions [15, 16]. Yet rather than replenishing the brain by restocking it with nutrients, the current favorite treatment method is some form of serotonin medicine, such as triptans for aborting an ongoing migraine, or serotonin reuptake inhibitors (SSRIs or SNRIs) for prevention for both migraines and depression. Many unlucky migraineurs and depression patients also receive a voltage dependent calcium channel blocker, one of which I discussed in my last article. Given that these medications are so often prescribed, one would think that they actually work. But do they?

They actually don’t work for depression over 70% of the time. And for migraines? Well, that is another story as I am about to discuss.  It is also important to note that where energy is needed, medicines that block energization via electrolytes actually work against recovery and dull the brain, using symptom management instead.

Why Triptans and SSRIs/SNRIs are Hit or Miss for Migraines

Serotonin for migraines only works sometimes and even then with tremendous side effects, often causing depression (see adverse reaction tables below), violence, and fatalities. Based on my migraine group where thousands of migraineurs have passed through over the years, the statistics show that 80% of those who join the group take some serotonin preventive, usually an SSRI or SNRI but they still need to take abortives, such as triptans, and yet they still have migraines! Not only does this show that serotonin does not work but also that there is a very dangerous practice of “more is better,” which may be followed by fatal consequences, such as serotonin syndrome. The dangerous practice is common because of five critical reasons:

  1. Doctors should know better than to prescribe multiple serotonin medications to the same patient and if they don’t know what their patients take, they owe the courtesy to ask before they prescribe!
  2. Pharmacies have records of all medicines a patient takes. If a doctor makes a mistake, it is the responsibility of the pharmacist to catch the mistake and warn the doctor and the patient. This has never happened in the entire history of my migraine group! I usually analyze their medicines and point out the pharmacological interactions and duplication that they print out and hand to their doctors. Only after the patient’s intervention will doctors initiate removal of dangerous medicines. Last time I checked: The patients are not responsible for the medicines they are being prescribed.
  3. 85% of the doctors do not recognize serotonin syndrome. The sad truth is that while 100% of the doctors can prescribe SSRIs and similar medications with a few scribbles, 85% of them do not recognize if it reaches toxic levels in their patients. I estimate that the majority of doctors are not familiar with the mechanisms of the medicines they prescribe; they cannot tell if one is a voltage dependent calcium channel blocker or a voltage dependent sodium channel blocker or both or neither.
  4. This is the saddest of them all: financial incentives actually cause many doctors to be angry with patients who wish to reduce their medicines. Many members in my migraine group faced rude and angry doctors who placed them on such quick reduction from these highly “discontinuations syndrome” (politically correct for addictive) medicines that they were forced back on the medicines and of course that increased again the lunches and dinners or straight cash flow of the prescribing doctors—search out your doctor’s name and see what she/he has been earning on your medicines in 2014!
  5. The side effects of many of these serotonin medicines are worse than the initial problem they are prescribed for; reduction is slow and painful. While the adverse effects hit all at once when starting a medicine, the very same adverse effects return in slow motion as the patients reduce. For example, they may not even realize that they had increased blood pressure, nausea, dizziness, and diarrhea all at once for a few days or weeks while starting the medication since these adverse effects showed up at once. But in reversing and stopping the medicine, each of these effects can last for weeks and is highly pronounced, frightening the patient. Furthermore, adverse effects are updated on the go by the FDA. Most users are not informed about these by their prescribing physicians.

I randomly picked two very common medications I see prescribed all the time. Zoloft, used for depression, is a selective serotonin reuptake inhibitor (SSRI), and Elavil, a tricyclic antidepressant (TCA), prescribed for migraines frequently. The list of side effects for Zoloft (Sertraline) is huge (Wikipedia). I must say that if I were not depressed before taking this medicine, I most certainly would be after reading this list:

Adverse effects: Fatigue, Insomnia, Somnolence (sleepiness), Nausea, Dry mouth, Diarrhea, Headache, Ejaculation disorder, Dizziness, Agitation, Anorexia, Constipation, Dyspepsia (indigestion), Decreased libido, Sweating, Tremor, Vomiting, Impaired concentration, Nervousness, Paroniria (i.e., depraved or morbid dreaming/nightmares), Yawning, Palpitations, Increased sweating, Hot flushes, Weight decrease, Weight increase, Myoclonus, Hypertonia, Bruxism (teeth grinding), Hypoesthesia, Menstrual irregularities, Sexual dysfunction, Rash, Vision abnormal, Asthenia, Chest pain, Paranesthesia, Tinnitus (hearing ringing in the ears), Hypertension (high blood pressure), Hyperkinesia, Bronchospasm, Esophagitis (swollen esophagus), Dysphagia, Hemorrhoids, Periorbital Edema, Purpura, Cold Sweat, Dry skin, Nocturia, Urinary Retention, Polyuria (excessive urination), Vaginal Hemorrhage, Malaise, Chills, Pyrexia (fever), Thirst, Pollakiuria, Micturition disorder, Salivary Hypersecretion, Tongue Disorder, Osteoarthritis, Muscular Weakness, Back Pain, Muscle Twitching, Eructation (belching), Dyspnea (air hunger), Epistaxis (nose bleed), Edema peripheral, Periorbital edema, Syncope, Postural dizziness, Tachycardia (high heart rate), Urticaria (hives), Migraine, Abnormal bleeding (esp. in the GI tract), Muscle cramps, Arthralgia, Depressive symptoms, Euphoria, Hallucination, Alopecia (hair loss), Urinary Retention (being unable to pass urine), Pruritus, Amnesia memory loss., Urinary incontinence, Eye pain, Asymptomatic elevations in serum transaminases, Abnormal semen, Melena (black feces due to a bleed in the stomach), Coffee ground vomiting, Hematochezia, Stomatitis (swollen mouth), Tongue ulceration, Tooth Disorder, Glossitis (soreness/swelling of the tongue), Mouth Ulceration, Laryngospasm, Hyperventilation (breathing more often than required to keep one’s blood sufficiently oxygenated), Hypoventilation (breathing less often than required to keep one’s blood sufficiently oxygenated), Stridor, Dysphonia (voice disorder), Upper Respiratory Tract Infection, Rhinitis (irritation/inflammation inside the nose), Hiccups, Apathy, Thinking Abnormal, Allergic reaction, Allergy, Anaphylactoid reaction, Face edema, Priapism, Atrial arrhythmia, AV block, Coma, Peripheral Ischemia, Injury, Vasodilation Procedure, Lymphadenopathy, Involuntary muscle contractions, Galactorrhea (lactation that is unrelated to pregnancy or breastfeeding), Gynecomastia (swelling of breast tissue in men), Hyperprolactinemia (high blood prolactin levels), Hypothyroidism (underactive thyroid gland), Syndrome of inappropriate secretion of antidiuretic hormone (SIADH), Pancreatitis (swollen pancreas), Altered platelet function, Hematuria (blood in the urine), Leukopenia (low white blood cell count), Thrombocytopenia (low blood platelet count), Increased coagulation times, Abnormal clinical laboratory results, Hyponatremia (low blood sodium), Conversion Disorder, Drug Dependence, Paranoia, Myocardial Infarction (heart attack), Bradycardia, Cardiac Disorder, Suicidal Ideation/behavior, Sleep Walking, Premature Ejaculation, Hyperglycemia (high blood sugar), Hypoglycemia (low blood sugar), Hypercholesterolemia (high blood cholesterol), Vasculitis, Aggressive reaction, Psychosis (hallucinations and delusions), Mania (a dangerously elated mood), Menorrhagia (an abnormally excessive amount of menstrual bleeding), Atrophic Vulvovaginitis, Balanoposthitis, Genital Discharge, Angioedema, Photosensitivity skin reaction, Enuresis, Visual field defect, Abnormal liver function, Dermatitis, Dermatitis Bullous, Rash Follicular, Glaucoma, Lacrimal Disorder, Scotoma, Diplopia, Photophobia, Hyphemia, Mydriasis, Hair Texture Abnormal, Neoplasm, Diverticulitis, Choreoathetosis, Dyskinesia, Hyperesthesia, Sensory Disturbance, Gastroenteritis, Otitis Media, Skin Odour Abnormal, QTc prolongation, Anaphylactoid Reaction, Allergic Reaction, Allergy, Neuroleptic malignant syndrome. A potentially fatal reaction that most often occurs as a result of the use of antipsychotic drugs. It is characterized by fever, muscle rigidity, rhabdomyolysis (muscle breakdown), profuse sweating, tachycardia, tachypnoea (rapid breathing), agitation, Stevens-Johnson syndrome a potentially fatal skin reaction, Toxic epidermal necrolysis another potentially fatal skin reaction, Torsades de pointes a potentially fatal change in the heart’s rhythm., Cerebrovascular spasm, Serotonin syndrome similar to neuroleptic malignant syndrome but develops more rapidly (over a period of hours instead of days/weeks for neuroleptic malignant syndrome), Bone fracture, Movement disorders, Diabetes mellitus, Dyspnea, Jaundice yellowing of the skin, mucous membranes and eyes due to an impaired ability of the liver to clear the haem breakdown by product, bilirubin, Hepatitis, Liver failure. This medicine can cause serotonin syndrome on its own.

For migraine I picked Elavil (Amitriptyline) which is a TCA. While it has fewer side effects (Wikipedia) than Sertraline (SSRI), one of its major side effects is headache. Why would a competent doctor prescribe a known headache causer to a migraineur?

Here are some of the other adverse effects: dizziness, headache, weight gain, delirium, confusion, anxiety, agitation, orthostatic hypotension (low blood pressure), sinus tachycardia, loss of libido, impotence, sleep disturbances such as drowsiness and insomnia. Most importantly, Amitriptyline inhibits sodium channels, L-type calcium channels, and voltage-gated potassium channels, and therefore acts as a sodium, calcium, and potassium channel blocker as well.

Recall my argument of a car only able to go on fumes for so long? This drug, by blocking all possible energizing channels, blocks the inflow of nutrients and the outflow of toxins. This car is not going anywhere!

Yet many migraineurs who join my group have been taking Elavil, which of course doesn’t work, so then they end up having to take several other medicines to replace activities the brain cannot do: they often receive prescriptions for other types of SSRIs, sometimes voltage dependent calcium blockers, barbiturates, NSADs, muscle relaxers, steroids and even triptans to come full circle, and add the very ingredient they blocked from being released the first place!

Does Serotonin Use Make Any Sense At All?

When a brain region is not able to generate action potential, as shown, lack of serotonin is not the cause. It is entirely possible that the particular neurons that cannot generate enough energy happen to be responsible for serotonin production, in which case adding serotonin will indeed take the pain away. However, it will not treat the underlying cause of not having enough energy for generating action potential. The fact that it is energy shortage rather than serotonin shortage that causes depression is clearly demonstrated by the deep brain stimulation experiments on live humans, where the voltage stimulation lifted their depression right there during the experiment without any serotonin. The patients were able to explain what they felt and how their depression lifted during the procedure [4-6, 17]. It all sounds very simple actually since we know what generates action potential in the brain: salt.

So why do migraine and depression sufferers keep on getting serotonin medications knowing that serotonin has absolutely nothing to do with migraines? This is a great question that I would like to ask many physicians! Habits are hard to break but eventually they must!

Concluding Thoughts

There is only a small chance that triptans or SSRIs will work for your migraines or depression but it is 100%  certain that adverse effects will prevent your brain from working properly. In the long run, these drugs cause permanent damage. Do yourself a favor and learn what migraines are and how to prevent them. Since migraines and depression have the same cause as seen in the scanners, why not try the same solution? Many who joined my migraine group with depression and migraine are now free of both, as well as all their medicines! Join the movement for healthy life without medicines.

Sources

  1. Gasparini, C.F., H.G. Sutherland, and L.R. Griffiths, Studies on the Pathophysiology and Genetic Basis of Migraine. Current Genomics, 2013. 14(5): p. 300-315.
  2. Young, W.B., et al., The Stigma of Migraine. PLoS ONE, 2013. 8(1): p. e54074.
  3. Holtzheimer, P.E., et al., Subcallosal Cingulate Deep Brain Stimulation for Treatment-Resistant Unipolar and Bipolar Depression. Jama Psychiatry, 2012: p. 150-158.
  4. Lozano, A.M., et al., A multicenter pilot study of subcallosal cingulate area deep brain stimulation for treatment-resistant depression. J Neurosurg, 2012: p. 315-322.
  5. Mayberg, H.S., et al., Deep brain stimulation for treatment-resistant depression, in Neuron. 2005. p. 651-60.
  6. Taghva, A.S., D.A. Malone, and A.R. Rezai, Deep brain stimulation for treatment-resistant depression. World Neurosurg., 2013: p. 826-831.
  7. Aurora, S.K., et al., Transcranial magnetic stimulation confirms hyperexcitability of occipital cortex in migraine, in Neurology. 1998. p. 1111-4.
  8. DaSilva, A.F., et al., tDCS-Induced Analgesia and Electrical Fields in Pain-Related Neural Networks in Chronic Migraine. Headache: The Journal of Head and Face Pain, 2012. 52(8): p. 1283-1295.
  9. Tepper, S.J., et al., Acute Treatment of Intractable Migraine With Sphenopalatine Ganglion Electrical Stimulation. Headache: The Journal of Head and Face Pain, 2009. 49(7): p. 983-989.
  10. Hadjikhani, N., et al., Mechanisms of migraine aura revealed by functional MRI in human visual cortex. Proceedings of the National Academy of Sciences, 2001. 98(8): p. 4687-4692.
  11. Charles, A.C. and S.M. Baca, Cortical spreading depression and migraine. Nat Rev Neurol, 2013: p. 637-44.
  12. James, M.F., et al., Cortical spreading depression and migraine: new insights from imaging? TRENDS In Neuroscience, 2001: p. 226-271.
  13. Lauritzen, et al., Clinical relevance of cortical spreading depression in neurological disorders: migraine, malignant stroke, subarachnoid and intracranial hemorrhage, and traumatic brain injury, in J Cereb Blood Flow Metab. 2011. p. 17-35.
  14. Bolay, H., et al., Intrinsic brain activity triggers trigeminal meningeal afferents in a migraine model. Nat Med, 2002. 8(2): p. 136-142.
  15. Pietrobon, D., Insights into migraine mechanisms and Ca(V)2.1 calcium channel function from mouse models of familial hemiplegic migraine. The Journal of Physiology, 2010. 588(Pt 11): p. 1871-1878.
  16. Vecchia, D., et al., Abnormal cortical synaptic transmission in CaV2.1 knockin mice with the S218L missense mutation which causes a severe familial hemiplegic migraine syndrome in humans. Front. Cell. Neurosci., 2015: p. epub ahead of print.
  17. Lozano, M. and N. Lipsman, Probing and regulating dysfunctional circuits using deep brain stimulation, in Neuron. 2013. p. 406-24.

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