The Inflammatory Response 

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You hit me - I'll hit you back!

When your immune system detects an injury, irritant, foreign body or attack to the body it simultaneously launches a rescue operation and a  counter-attack.

This is called the inflammatory response.

The immune system launches chemicals to the area to protect it, repair it and get rid of the irritant or foreign undesirable. It also warns the brain to take measures to ensure these take place.

4 main features characterise the inflammatory response, these being:

S - Swelling

H - Heat

R - Redness

P - Pain

This process is one of our body’s most important ways of protecting us from things that it perceives are causing us harm..

A major problem is low levels of inflammation which smoulder away inside us. It is often difficult to detect, and might be deep inside our bodies. The inflammation may be triggered by food sensitivities, chemical sensitivities, environmental changes, hormone changes, musculo-skeletal injuries, infections, dehydration or a wide range of other things.

But regrettably, in some people inflammation occurs in unhelpful ways, and for many this means migraines.

It is sometimes triggered when unwarranted or when the body reacts more strongly to a threat than it should, i.e. reacting inappropriately or disproportionately to a trigger.

And some people are genetically more sensitive to triggers so that low levels of 'smouldering' inflammation caused by one or more of a myriad of triggers anywhere in the body, then lead to the release of more chemicals which can then bring on a migraine.

HOW  might inflammation lead to a migraine?

There are many processes that take place during inflammation, and as a result, there are different theories that suggest a number of these specific processes might cause a migraine.

Some of the main theories put forward by researchers include:

  1. Blood vessels expanding (vasodilation) and/or
  2. Blood vessels contracting (vasocontraction)
  3. Dysfunction and disruption in the brain cells (neurons and neurotransmitters)
  4. Dysfunction and disruption in the hormones
  5. Dysfunction and disruption of the immune system

It is likely that a number of these processes in combination cause migraines, and that every migraine sufferer is affected by some more than others.

While early theories pointed to vascular causes, (i.e. blood vessels expanding and/or contracting in the brain), nowadays most researchers postulate that migraine specific triggers cause brain dysfunction which then causes the trigeminal nerve to release chemicals (called neuropeptides and neurotransmitters) resulting in an inflammatory reaction and pain in the sensory fibres of the trigeminal nerve/s.

At the same time the inflammatory response releases a cascade of other chemicals that bring on pain.

Whatever the causes what is crucial for the migraineur is to try to identify their triggers and avoid them

Nonetheless, let’s take a look at some of the underlying processes that researchers think might be involved in migraines.

Do blood vessels shrinking or swelling cause migraines?

Shrink or Swell?

For many decades most mainstream researchers attributed migraines to either:

  1. blood vessels swelling and expanding (known as vasodilation; vaso = blood vessels) or to:

  2. blood vessels shrinking and constricting (vasoconstriction) in reaction to certain inflammatory stimuli.

In other words it was generally believed that migraines were caused these vascular mechanisms, these being changes in blood cells.

Modern researchers now generally accept that migraines are primarily a neuronal dysfunction (brain cells).

We mention the vasodilation and vasoconstriction theories because there is still considerable mention of them, and they are a major part of the migraine process, but are generally accepted as not being the cause.

Vasoconstriction in Migraine

Vasoconstriction is seen in some cases of migraine. When the blood vessels constrict, less blood gets to areas of the brain so less oxygen and less nutrients are delivered. 

Vasodilation in Migraine

Vasodilation, where arteries widen and expand, allows more blood to flow into those areas of the body. Some experts think vasodilation occurs as a result of an initial period of vasoconstriction – in other words, first the blood vessels contract causing a restriction in the blood supply, which then triggers vasodilation.

Most experts now believe the blood vessel changes that have been observed in migraine sufferers are a secondary result of migraine and not a primary cause. For example, the vascular theories of migraine were strongly refuted by Dr Peter Goadsby in 2009. (Goadsby, 2009) 

Migraine Pain starts in the Brain

Research over the last 20 years points to the cause of the PAIN in migraine starting in the brain cell (neuron).

The brain cell is the basic working unit of the brain whose job is to send out and receive information. 

These neuronal signals are in the form of neurotransmitters  there are many different types including those made of amino acids and peptides (the building blocks of proteins). These signal information to and from neurons via nerves and other cells, to tissues and muscles all around the body.

Peptides - neurotransmitters that may cause migraine pain

When a neuron senses an attack on the body, whether it be from a knife slicing your skin, being clubbed with a baseball bat, a poison, or a food to which you are allergic that neuron launches a rescue mission and a counter-attack, sending out chemical signals to the affected parts of the body.

It does this by releasing amino acids called peptides. A peptide from a neuron (brain cell) is called a neuropeptide.

A deal of modern research points to the main culprit in migraines being the Calcitonin Gene-Related Peptide (CGRP). (Durham P. L., 2006) (Bigal, Walter, & Rapoport, 2013)

 At the same time as CGRP is synthesised and released other chemicals are expressed and sent to the injury site in the inflammatory response.

This process is often going on somewhere deep in the body caused by low level inflammation.

These other chemicals include arachidonic acid, prostaglandins, cooxygenase 1 and 2, thromboxanes and others. 

Prostaglandins

One group of chemicals that is released are called prostaglandins. Prostaglandins are lipids (|fats) that the body synthesises and releases as part of the inflammmatory response when it detects infection, injury, tissue damage.

Prostaglandins contribute to the development of the signs of acute inflammation. (Ricciotti & FitzGerald 2011).

They are important because they play a key role in the inflammatory response, as well as being involved in controlling blood flow and blood clotting.

Prostaglandins cause vasodilation, preventing unnecessary blood clot formation and also control the muscle contraction.

They catalyze the conversion of arachidonic acid to the endoperoxide prostaglandin which can form a variety of prostaglandins, thromboxanes and prostacyclin. (van Breeman, Tao, Li 2011) (Ricciotti & FitzGerald 2011).

When injury occurs prostaglandins are produced and released by an enzyme called cyclooxygenase 2 or COX-2.

COX-2 is released specifically during the inflammatory process and with  COX-1 is essential for proper functioning of the gastrointestinal tract and kidneys.

Many drugs have been designed and used to block the release of COX-2, and thus, for many people, block the inflammatory process, and the pain associated with it.

Certain constituents of the hundreds in ginger, such as 10-gingerol, 8-shogaol and 10-shogaol also carry out the same function, courtesy of Mother Nature, and in a manner which is gentle on the human kidneys and liver.

Migraine Escape® contains 10-gingerol, 8-shogaol and 10-shogaol and these substances were shown to inhibit COX-2 in research conducted by Department of Medicinal Chemistry and Pharmacognosy, University of Illinois College of Pharmacy, Chicago, USA. (van Breeman, Tao, Li 2011)

 

Thromboxanes

On the other hand, thromboxanes (produced by platelet cells) are vasoconstrictors that cause blood clotting (platelet aggregation). Their name comes from their role in clot formation - thrombosis.

Many drugs reduce pain by blocking thromboxane (e.g. aspirin) and prostaglandin.

Interestingly research shows that ginger also has the ability to block the release of  thromboxane and prostaglandins providing one of several explanations for how ginger has come to be used for thousands of years in the treatment of pain relief, particularly in the case of migraine. (Mustafa & Srivastava, 1990)

Going back to the CGRP that is associated with migraine…

CGRP seems to be being singled out as the main chemical cause of the pain associated with a migraine.

CGRP is also identified by researchers as a potent vasodilator. ( Brain, Williams, Tippins, & Morris, 1985)

Research studies by Dr Paul Durham at the Missouri State University showed that CGRP is released from ganglia cells in the trigeminal nerve. (Durham P. L., 2006)

Ganglia are clusters of nerve cells, and the trigeminal nerve controls feeling in the face transmitting feelings such as touch, heat and cold, and pain from the face to the brain.

The trigeminal nerve also controls the facial muscles involved with biting and chewing.

 

It seems that when one or more of the trigger factors discussed earlier combine together, the trigeminal nerves release CGRP.

The CGRP then causes the expression of even more inflammatory peptides and chemicals (sometimes referred to as mediators) - some with wonderful names like tumor necrosis factor-α (TNF-α)!

These mediators can act to activate more CGRP synthesis over hours or even days, leading to the pain of the migraine.

As previously stated, for some people finding source of inflammation is easy, for some it comes with a process of self-evaluation, but for many they just cannot locate it.

If you're one of those people who cannot find the source, one common action is to reduce the inflammation, and you likely already do (or have tried) this through your use of ANTI-INFLAMMATORY migraine drugs.

A big family of these are Non-Steroidal Anti-Inflammatory Drugs or NSAIDs.

The triptan family (including sumatriptan) and painkillers like ibuprofen and aspirin are examples of these.

So can we not just block the release of the CGRP?

Good point!

That is exactly where the current research is now concentrating, and the big pharmaceutical companies are spending millions on developing drugs to stop the release of the CGRP, and or the other chemicals that are involved in its synthesis and release. (Durham P., 2008 Sep)

How can they achieve this?

Well, 4 big pharmaceutical companies are carrying out trials of new drugs that do just that. Media reports that the price of these treatments could be around $8,500. (Court, 2017)

We will have to wait for their release… but… you do not have to wait because...

University research shows that GINGER can reduce the release of CGRP

Interestingly enough recent research published by a team from George Mason University, Virginia shows that ginger is one natural compound that reduces CGRP release. (Slavin, Bourguignon, Jackson & Orciga, 2016)

And ginger is the key component in Migraine Escape (ginger which is extracted using a specialised process so that it is especially concentrated).

So interestingly, this university research gives us strong scientific basis for understanding how Migraine Escape works (in light of the most recent research at time of writing - September 2017).

We already know that ginger has a long history in the treatment of migraines for thousands of years and know from many research papers that it is has been successful in the treatment of migraines.

We have also seen how it works with many people using Migraine Escape to reduce their migraines*.

The George Mason University study stated that results showed "… a statistically significant decrease in stimulated CGRP secretion from (neuroendocrine ) CA77 cells following treatment with ginger (0.2 mg dry ginger equivalent/mL).

Relative to vehicle control, CGRP secretion decreased by 22%.

They also stated that "Interruption of calcium signalling, a mechanism which can trigger CGRP release, has been suggested as one potential route by which exogenous food substances may impact CGRP secretion" and concluded that "...ginger extract showed inhibition of calcium influx."

So how does Migraine Escape compare to this study?

Well Migraine Escape is highly concentrated ginger extracted using a unique and high-tech process. The liquid is applied topically, that means it is rolled on the forehead.

Why apply it topically? Why roll it on?

Because topical application can be a far more effective way to get the active ingredients into the bloodstream, and more and more modern medicines and treatments are tending to topical application as it can be less stressful on organs such as the kidneys.

Inflammation is implicated in most migraine… and ginger is a powerful anti-inflammatory

Ginger works on several levels... not only reducing the release of the peptides such as CGRP, but also it acts as an anti-inflammatory i.e. the same mode of action used by triptan migraine drugs.

Yes, ginger is one of nature's anti-inflammatories, and is a plant with extraordinary qualities.

There is an abundance of evidence of ginger's medicinal properties and in time we will be exploring in full how these relate to migraine.

We at Migraine Escape will continue our findings to add to this website and page, and will continue to try to summarise the mountains of research into layman's terms. We will add links to pages with more details on the myriad of individual topics that are covered above.

So don't forget to keep checking back for updates!

References on Migraine Causes

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