Posts Tagged ‘cortical spreading depression’


Migraines (Part 4) (Last Edited: 2009 Nov 19)

2008 August 23

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This is the final part of a four part series about migraine. You can use the links above or at the end of this page to go back. Or you can jump to any part from the Migraine FAQs page link.

There is difference of opinion over the exact mechanism for migraine pain. Both agree that the trigeminal nerves, that registers pain, are central to the mechanism. These relay pain signals to the thalamus. The thalamus processes them and then passes information to the cerebral cortex that registers it as pain. But the mechanism for pain signal generation in the trigeminal nerve differs between the two theories.

One school suggests that the cortical spreading depression directly stimulates the trigeminal nerves through the release of neurotransmitters and ions as the wave spreads. These then stimulate the trigeminal nerves to register pain. There is evidence supporting this mechanism, even in patients who do not necessarily experience aura during the spreading depression. This is also supported by the observation of increased, then decreased, blood flow in migraine without aura. This theory also helps explain vaguer symptoms observed such as fatigue or difficulty concentrating.

The second school places the cause of pain in the brain stem. This is the control centre for pain sensitivity, as well as other functions. Positron-emission tomography (“PET scans”) during migraine attack show that three clusters of cells called “nuclei” are active during and after migraine. This school suggests that abnormal activity here induces two pathways to pain. These nuclei normally inhibit the trigeminal nerves, reducing pain sensitivity. The nuclei’s misbehaviour may activate the trigeminal nerves causing them to fire and register “phantom pain”. It is suggested the nuclei may even trigger cortical spreading depression. These nuclei also control the flow of sensory information like light, noise and smell. Misfiring in the nuclei may explain the sensitivity to these during some migraine attacks.

There is also a minority opinion that migraine begins in neck pain.

The activity of the nuclei are also changed by behavioural and emotional states, which are also accepted as possible migraine triggers. The nuclei receive input from only two parts of the cortex; those that regulate arousal, attention and mood. These links could explain the mood fluctuations sometimes observed during migraine and the statistical association between migraine, depression and anxiety disorders.

The neurotransmitter serotonin seems to play some role in migraine. It also plays a part in mood regulation and in anxiety disorders and depression. Its role in blood vessel dilation may be important. Triggers like stress, bright lights, dehydration and so on are thought to increase serotonin levels in the brain. This disrupts the normal functioning of the hypothalamus and may trigger the blood vessel changes in migraines. Studies have shown how injection of a drug called reserpine, that releases serotonin, induces migraine headaches in sufferers, but not other people.

Both these new approaches may eventually offer relief for migraine sufferers. At present, few drugs can prevent migraine. None of the drugs used today were developed specifically for migraine. Only around one in two sufferers are helped by them and the potential side effects can be serious. Those that tend to be most effective, anti-hypertensives, anti-epileptics and antidepressants, have all been shown to inhibit cortical spreading depression. This supports the theory that this neural phenomenon contributes to migraine both with and without aura. New drugs are now in development that target “gap junctions” – a type of ion channel – effectively halting calcium flow between brain cells.

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MacGregor, Dr Anne. 2005. Understanding Migraines and Other Headaches. Family Doctor Publications Limited/British Medical Association


Migraines (Part 3) (Last Edited: 2009 Nov 19)

2008 August 16

Go back to Part 2 | Go on to Part 4

This is part three of a four part series about migraine. You can use the links above or at the end of this page to go back or forward. Or you can jump to any part from the Migraine FAQs page link.

The exact triggers for migraine attack are uncertain, and may vary widely. Sufferers usually keep a diary to try to identify:

  1. Triggers,
  2. Other things affecting migraine frequency,
  3. Things that may prevent attacks,
  4. Things that might predict impending attack.

Commonly suggested triggers include: allergies, things in the environment like lighting, noise or scents, stress, changes in sleep patterns, cigarette smoke, alcohol, certain foods, and weather or seasonal changes.

All auras are the results of “cortical spreading depression”. This is a self-propagating wave of cell depolarisation that travels through the cortex. The cortex is the crinkled outer or “higher” part of the brain. During this phase, the affected neurons go into a kind of hibernation. The exact mechanism of neuronal “firing” depends on a critical flow of sodium, potassium and calcium ions. During the depressed state, neurons rest high in potassium, and low in sodium and calcium. Cell “firing”, releases neurotransmitter chemicals, when the inside of the cell is positively charged relative to the outside. After firing the cells become strongly negatively charged on the inside by allowing potassium ions to flow out. This returns the neurons to their resting states. But neurons can become hyper-polarised, or inhibited, for some time after intense stimulation.

The phase of hyper-excitability followed by inhibition in cortical spreading depression may explain the changes in blood blow recorded before the pain phase of migraine. Active neurons need energy, which is transported by blood. When inhibited, they need less blood.

Further studies link cortical spreading depression with description of visual aura. The wave travels across the cortex at between two and three millimetres per minute. The visual aura match with those expected given that rate of spread. The change of sensations also match observed spreading depressions.

Migraine is a complex disorder that shows a strong genetic component. But studies show that it is a range of genetic mutations that affect migraine rather than a single gene. This is called a poly-genetic disorder. There is also evidence of non-genetic parts. The strongest evidence for both comes from identical twin studies. These show that identical twins are more likely to share migraine that non-identical twins. But even identical twins do not necessarily both share migraine. One may suffer migraine, while the other does not.

Recent evidence also supports the view that at least one type of migraine is caused by faulty genes. These govern the ion channels talked about earlier. This is a newly recognised condition called “channelopathy”, which is also responsible for other conditions like cardiac arrhythmia and seizures. But it is not yet known whether this mechanism is common to all forms of migraine.

There is also another controversial theory about a common heart defect. It is called “patent foramen ovale” or PFO. It is where a small hole in the heart allows oxygen-rich and oxygen-poor blood to mix. It is controversial because the way PFO may cause migraine is unclear. Closing the hole in migraine patients has shown some results, but they are not statistically significant.

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Migraines (Part 1) (Last Edited: 2009 Nov 19)

2008 August 2

This is part one of a four part series about migraine. You can continue to part two from the link at the bottom of this page. Or you can jump to any part from the Migraine FAQs page link.

In this series I have used reputable sources for the science of migraine. I’ll include the sources in the final post.

Key Facts

  • Migraine is more than a headache: it can be intensely painful and has distinct phases.
  • The disorder used to be considered a vascular one. But recent research reveals it to be neurological. It is now known to relate to a wave of nerve cell activity that sweeps across the brain.
  • The root of migraine may be in brain stem malfunctioning.
  • Although debate swirls about the precise cause of migraine, discoveries are already allowing the development of new treatments

1. “There’s no such thing as migraine.”

Worldwide more than 300 million people suffer migraine attacks. The condition is in the historical record, suggesting it is at least 7,000 years old. Yet it stays misunderstood generally, and is often poorly treated by the medical profession. There are still doctors who, like a section of the general public, dismiss migraine as a condition.

The annual cost to the US economy alone from lost work, welfare payments and health care costs is $17 billion. But modern medicine is beginning to make inroads into migraine, with new discoveries in genetics, brain imaging and molecular biology.

Part of the problem is that there appears no one condition as such. The average frequency of attacks for sufferers is one to two per month. But ten percent suffer weekly migraines, twenty percent experience migraines for two to three days. Up to fourteen percent have more than fifteen migraines per month (one every two days on average).

There is no single trigger for migraine generally. Listed triggers include alcohol, dehydration, exercise, menstruation, stress, weather or season changes, and on and on. Women tend to be more prone to migraine than men, but migraine occurs in both sexes. The peak age range for women lies between fifteen and fifty-five.

It used to be a leading theory that migraines were a physiological result of lowered blood flow in the brain. Recent evidence is now discounting this theory. Migraine is now seen as a disorder of the nervous system, arising from the brain stem. Studies of brain activity during migraine attack have proven scientifically that there are at least three key effects:

  • Cortical spreading depression.
  • Blood vessel dilation, followed by constriction.
  • Activity in three bundles of nerves, or “nuclei”, in the brain stem.

As well as these, genetic studies into predisposition to migraine show genes play a part. All this means that there is ample scientific evidence supporting the real existence of the condition. Not that sufferers need any convincing. A recent study found that the nerves carrying pain signals are 21% thicker in migraine sufferers than other people.

Go on to Part 2