Migraine: calm the nerve cells by feeding them a body’s own substance: from stress to relax
Standing on shards of glass. Her feet had been extremely painful for almost a year already, as if she was standing on shards of glass. The cause? Diabetes. In case of diabetes, the nerve fibers are so tormented that they almost exclusively give off pain signals, this causes painful and burning sensations in the feet.
The neurologist had tried everything but the pain hardly decreased while the side effects made her very drowsy. She started treatment with a supplement that was quite new in the Netherlands, called PeaPure (400 mg capusles) ( The Italian product Normast (300 and 600 mg tablets contains the same PEA). PeaPure contains palmitoylethanolamide without excipients, which we will elaborate on later.
The fascinating thing is that this substance is produced in our own body by our cells and it is an effective pain reliever. It has been used to treat many thousands of patients successfully. There are no know side effects and the substance can therefore be safely combined with other pain medicine and treatments.
Fortunately this substance was able to finally help her and the pain decreased significantly over the weeks. During her fourth visit she looked particularly happy because something special had happened, het migraines had become less severe as well. For this reason it’s worth it to discuss migraines and how this substance not only helped her get rid of the sharp burning pain but also for the most part rid her of her migraines.
Migraine: unrest in the brain
We all have a friend of family member who regularly suffers from extreme headaches, sometimes even accompanied by nausea that could lead to vomiting. There are remedies against migraines but despite those there’s not much more a migraineur, as people suffering from migraines are called, can do than accept the suffering and hope it passed quickly.
It always passes, but not always as quickly as you’d like. It can take you out for days. For this reason, migraineurs are looking for solutions. As far as medicine is concerned there are only 2 solutions. Either you look for drugs to relieve the attack, like aspirin and more current triptans, or you take chronic measures to prevent the attacks. Unfortunately the ideal remedy has not yet been found.
The general assumption is that the cause of these severe pains lies in the nerve cells within the brain. It is believed these cells become overactive and give off pain signals for hours or days. This is mostly correct, but not entirely, and that’s where an opportunity can be found to develop a new treatment.
It’s not the nerve cells that play the most important role, but a type of connective tissue cell that surrounds and feeds the nerve cell. These cells form a type of lining around the nerve cells. Together these cells form the glia tissue. And in that glia tissue lies a possible new solution for migraine treatment. In case of migraines, the glia tissue is in a constant state of stress and produces all sorts of nervous substances that stimulate the nerves.
The question is, how to we calm the glia tissue?
But before look closer at the glia tissue, let’s go back to the brain and migraine.
Brain in stress
The brains of people with migraines are programmed differently than people without migraines and bursts in to stress easier. In technical terms this is called sensitization. Simple stimuli, that in normal circumstances are hardly noticeable, are amplified with central sensitization. A little bit of light turns in to painfully light, a soft sound turns very loud and a gentle touch can create a severe response. People who experience migraines often prefer to stay alone in a dark place until it passes.
Silence, darkness, the least amount of stimuli possible. Because every stimulus is amplified by the stressed brain, even scents can be too much during an attack. The question is, what is hiding behind this stress? What mechanisms keep the brain in a constant state of amplified stimuli? And how can we bring the brain back in to a relaxed state?
Current insights in to what hides behind the phenomenon of central sensitization, leads to an entirely new approach of migraines. In our practice we have seen some fine examples of this. There is no brake: the cells are on a rampage. In case of migraine there is no brake.
Small stimuli are experienced as strong and during an attack you want to crawl away in a small hole somewhere. Where is the brake? Through current research on brain function we know that this brake is situated somewhere in the brain stem, which is part of what we call the central grey. It is a part of the brain stem that is situated around a channel with cerebrospinal fluid called the aqueduct. Because there is gray matter surrounding the aqueduct we also refer to this part of the brain as the periaqueductal gray, PAG.
Situated in the PAG are the cells that inhibit regular incoming stimuli, so you don’t get stressed about everything. One of the consequences of when the stimuli do rampage freely in to the brain is that the brain swells up a little bit. This swelling is another stimulus that gets amplified so you experience a throbbing headache.
The throbbing is present in everyone’s head, but normally we don’t feel it because the perception of the throbbing is inhibited by the cells in the PAG. The nerve cells become over stimulated and to inhibit that over stimulation substances like triptans were developed.
These substances inhibit a certain neurotransmitter system which is related to serotonin and that’s why the nerve cells calm down a bit and the migraine disappears. But if you think this through you’re only inhibiting the over activity without normalizing the central brake in the PAG.
That brake is made up out of nerve cells that are in a state of central sensitization. To restore that brake we have to focus on calming the lining of the nerve cells, the glia cells.
On every nerve cell ten glia cells: the reason for excitement
Everyone used to think that if you really wanted to understand the working of the nervous system, you specifically have to look at the nerve cells. The other connective tissue cells around the nerve cells were only thought to be a kind of glue to keep the nerve cells in place. However, nothing is further from the truth.
The cells are called glia cells, glia meaning glue, but since several years we have started to understand that these cells are much more important than we thought. Only the fact that there nerve cells are surrounded by 10 glia cells should make us think. And that finally happened. The entire case of central sensitization is maintained by a disturbed metabolism in the glia cells.
During chronic pain, these cells are so hyperactive that they will start to produce and secrete all sorts of substances that agitate the nerve cells. Growth factors is an example of this.
That sounds all right, but due to the work of the Italian professor Rita Levi-Montalcini we understand more about the growth factors. It’s this type of small protein molecule that, together with an army of other substances, is secreted by the glia cells during chronic pain. The nerve cells get aggravated as they are basically bathing in those substances when this happens. When the nerve cells are aggravated they will give off wrong or increased signals, which are pain signals.
This is how both glia cells and nerve cells shoot in to overdrive. On top of that, because of all the growth factors from the glia tissue, the nerve cells will start to produce substances like neurotransmitters, which cause great stress in all the nearby cells. This is called winding up and forms the condition of central sensitization. From a wound up state to a chilled out state: palmitoylethanolamide, the chill molecule.
Professor Montalcini, who got to live to 102 years of age with a clear mind and still active in science, discovered that it’s possible to calm all the stress in the brain due to chronic pain with a natural pain reliever. A simple fatty molecule produced by every cell in our body. It’s a natural bodily substance.
On top of decreasing the pain, this molecule also works as an anti-inflammatory. This is a double benefit, because the molecules that are secreted by the glia cells and irritate the nerve cells are a kind of inflammatory factors, which in turn are inhibited by this substance too.
The substance has a difficult name: palmitoylethanolamide. We will continue to call it PEA. Our own nerve cells and surrounding cells produce this pain relieving and anti-inflammatory substance during chronic pain. It is our own natural painkiller. A small Italian scientific organization followed the directions of professor Montalcini and first developed a tablet containing PEA. Now a supplement is available in capsule form that can be given to patients with severe pain in whose cases no other remedy seems to help. The brand name is PeaPure (capsules) or Normast (tablets).
PEA: who has been treated?
In the mean time thousands of patients have been treated with this substance and often with very impressive results. PEA showed to decrease pain after multiple sclerosis, severe back pains, hernia pain, shingles, pain from pinched nerves like the carpal tunnel syndrome and pain due to diabetes, just to name a few. For this reason we give PEA a green light for the treatment of pain. It looks like this substance can also offer relief for migraines.
PEA is available in the Netherlands as the supplement PeaPure and in Italy as the tablet Normast. Both are made according to the highest quality requirements.
Dosing and the use of PEA for migraines
Start with 1200mg of PEA per day, divided over the morning and evening after meals. PeaPure comes in 400mg capsules. If the pain decreases after 2 months you can change to one capsule twice a day. During a migraine attack, take an extra capsule by opening it and placing the powder under the tongue to let it melt.
In case the pain comes back, increase the dose back to 1200mg per day. If the migraines don’t get less after 2-3 months it makes no sense to keep using this substance.
Jasmin, luc et al. Can satellite glial cells be therapeutic targets for pain control? Neuron gliabiology 2010Dodick D, Silberstein S. Central sensitization theory of migraine: clinical implications. Headache 2006;46(Suppl. 4):S182–91.
Weiller C, May A, Limmroth V, et al. Brain stem activation in human migraine attacks. Nat Med 1995;7:658–60.
Goadsby PJ, Lipton RB, Ferrari MD. Migraine–current understanding and treatment. N Eng J Med 2002;346:257–70.
Watkins LR, Milligan ED, Maier SF. Glial proinflammatory cytokines mediate exaggerated pain states: implications for clinical pain. Adv Exp Med Biol 2003;521:1–21.
Egger J, Carter CM, Wilson J, Turner MW, Soothill JF. Is migraine food allergy? A double blind controlled trial of oligoantigenic diet. Lancet 1983;2:865–9.
Hernia pain en Normast Diabetic neuropathic pain  
Carpale Tunnel Syndrome en Normast 
 G. Guida, A. de Fabiani, F. Lanaia, A. Alexandre, G.M. Vassallo, L. Cantieri, M. de Martino, M. Rogai, S. Petrosino | La palmitoiletanolamida (Normast) en el dolor neuropatico cronico por lumbociatalgia de tipo compresivo: estudio clinico multicentrico. | Dolor | 2010, 25:35-42
 Biasiotta A, La Cesa S, Leone C, Di Stefano G, Truini A, Cruccu G. | Efficacy of palmitoylethanolamide in patients with painful neuropathy. A clincial and neurophysiological open study. Preliminary results. | , Volume 4, Issue 1, May 2010, Page 77.
 Matias I, Wang JW, Moriello AS, Nieves A, Woodward DF, Di Marzo V. | Changes in endocannabinoid and palmitoylethanolamide levels in eye tissues of patients with diabetic retinopathy and age-related macular degeneration. | Prostaglandins Leukot Essent Fatty Acids. |2006 Dec;75(6):413-8. Epub 2006 Oct 2.
 Assini A, Laricchia D, Pizzo R, Pandolfini L, Belletti M, Colucci M, Ratto S. | P1577: The carpal tunnel syndrome in diabetes: clinical and electrophysiological improvement after treatment with palmitoylethanolamide | Eur J Neurol | 2010: 17(S3):295.
 Sarchielli P, Pini LA, Coppola F, Rossi C, Baldi A, Mancini ML, Calabresi P. | Endocannabinoids in chronic migraine: CSF findings suggest a system failure. | Neuropsychopharmacology. | 2007 Jun;32(6):1384-90. Epub 2006 Nov 22.
 Levy D. | Migraine pain, meningeal inflammation, and mast cells. | Curr Pain Headache Rep. |2009 Jun;13(3):237-40.
 Blanco I, Béritze N, Argüelles M, Cárcaba V, Fernández F, Janciauskiene S, Oikonomopoulou K, de Serres FJ, Fernández-Bustillo E, Hollenberg MD. | Abnormal overexpression of mastocytes in skin biopsies of fibromyalgia patients. | Clin Rheumatol. | 2010 Dec;29(12):1403-12. doi: 10.1007/s10067-010-1474-7. Epub 2010 Apr 30.