Vitamin D could save the country about €37.5 billion in health care costs, according to a new review  of professor A. Zittermann.

Vitamin D receptors are expressed in many other tissues beyond the musculoskeletal system, and vitamin D plays protective physiologic roles against several chronic diseases such as cancer, osteoarthritis, diabetes, and cardiovascular conditions. There is clear evidence for an association between low vitamin D status and pain in the general population. The chronic pain syndromes included chronic back pain, chronic musculoskeletal pain or widespread pain, and polymyalgia and in all these cases vitamin D was suggested as the cause of such nonspecific pain.

Vitamin D through its receptor modulates neuronal differentiation as well as neuronal growth and function. In rats, the production of nerve growth factor which is required for the development and survival of both sympathetic and sensory neurons decreases in the presence of vitamin D deficiency. In fact, in vitamin D deficient diabetic animals correction of vitamin D deficiency resulted in an improvement in nerve growth factor production. Decrease in neurotrophins and defective calcium homeostasis leaves the nerve vulnerable to toxins including hyperglycemia. As a result, a deficiency of vitamin D impairs nociceptor function, worsens nerve damage, and lowers the pain threshold.

And: 

In another study vitamin D levels were not only inversely proportional to a neuropathy symptoms score but also showed a statistically significant (OR 3.47 95% CI 1.04–11.56 P = 0.04) association with slower nerve conduction velocities after correction for duration of diabetes and levels of HbA1c, LDL, and urinary albumin. 

Two qoutes from a recent report were a patient suffering from severe neuropathic diabetic pain, refractory to analgesics, experienced cler pain relief after the correction of the vitamine D deficiency. 

Normast, Pelvilen, PeaPure: we will discuss some differences and similarities of these three nutraceuticals. Palmitoylethanolamide is the active ingredient in all three. Normast is the Italian branded nutraceutical, available in Italy probably since 2007. Normast was developed since the end of last year, and the name Normast refers to the normalization of mast cell hyperactvity. The brandname Normast has been created in 2005.

Normast is the brand name of the in Italy produced palmitoylethanolamide version, Pelvilen consists of 400 and 200 mg tablets, and PeaPure is a brand introduced in 2012 by the company Russell Science Ltd, produced in the Netherlands.

Physicians from the Institute of Neuropathic Pain in the Netherlands reported this week a breakthrough in the treatment of severe pain in Sudeck's dystrophy. Sudeck's dystrophy, or Chronic Regional Pain Syndrome (CRPS) is a severe disorder, which can arise after a fracture or distorsion. After a freacture or distorsion a severe swelling can occur, which makes the use of the hand or foot impossible. Pain is severe and very difficult to treat.  

The breakthrough has been discussed in an open access, international pain journal.  Some years ago, it became clear that the cause of Sudeck is a neuro-inflammation. Physicians in the Netherlands developed a new treatment based on a natural, endogenous molecule and supplement, PeaPure. Palmitoylethanolamide is the active ingredient of this supplement.

The mechanism of action of palmitoylethanolamide has been discovered in 1993 by the Nobel prize laureate professor Rita Levi-Montalcini. Since 1993 this compound has veen explored in many clinical trials, and proved to be effective and safe. Now it appears severe pains in Sudeck's dystrophy respond well to the treatment with palmitoylethanolamide. The severe edema (swelling) also vanished after treatment.

PeaPure thus appears to be a new, effective and safe treatment for Sudeck. 

The article has appeared in the 'Journal of Pain Research' with the title:Treatment of chronic regional pain syndrome type 1 with palmitoylethanolamide and topical ketamine cream: modulation of nonneuronal cells.   

Abstract: Chronic regional pain syndrome (CRPS) can be intractable to treat and patients sometimes suffer for many years. Therefore, new treatment strategies are needed to alleviate symptoms in CRPS patients. This case report describes a patient suffering from intractable CRPS type 1 for 13 years. Due to her swollen painful feet and left knee she is wheelchair-bound. The combination of palmitoylethanolamide and ketamine 10% cream reduced her pain by more than 50% after 1 month of treatment, and a marked reduction in swelling and skin discoloration was noticed. Furthermore, she could walk independently again and she experienced no side effects.

Thus, palmitoylethanolamide and topical ketamine could be a combination therapy option for treating CRPS patient

Source:Keppel Hesselink JM, Kopsky DJ Treatment of chronic regional pain syndrome type 1 with palmitoylethanolamide and topical ketamine cream: modulation of nonneuronal cells. Journal of Pain Research 2013:6 Pages 239 - 245 

Case description

A 53 year old famale patient suffered from diabetes type II since more than 10 years. She developed severe pains at the age of 48 and was totally refractory for many analgesics. Prescription of gabapentine, amitriptyline, pregabalin and carbamazepine remained unsuccesful in reducing her pains. On the numeric rating scale (NRS) for pain she scored 8 over 10.

She was a candidate for a spinal cord stimulator and wished first to follow our treatment protocol for treatment-resistant neuropathic pains, based on palmitoylethanolamide (Normast, PeaPure).

Pharmacologic Treatment of Central Post-Stroke Pain By:  A. Frese, I.W. Husstedt, E.B. Ringelstein, and S. Evers:  ClinJ Pain 2006;22:252–260: 

Treatment Recommendation for CPSP Based on Evidence Level

Short term pain control: Lidocaine IV 5 mg/kg over 5 minutes

Propofol IV (Gaba-ergic) 0.3 mg/kg per hour  

Oral treatment: Drugs of first choice(based on controlled trials):  

amitriptyline(anti-depressant) at least 75 mg per day

lamotrigine(glutamatergic) (at least 200mg per day

Drugs of second choice(based on open studies and experts’ opinion):

Mexiletineupto10 mg/kg per day

Fluvoxamin up to 125mg per day

Gabapentinat least 1200mg per day

Kahler's disease is cancer of certain white blood cells, the plasma cells, and leads to death, mostly within 3-4 years. It is the second most frequent occuring forms of blood cancer, after non-Hodgkin's disease. Initially patients can respond to chemotherapy, but treatment resistance often occurs. Furthermore, side effects such as nerve pain and nerve disfunctions (painful neuropathy) are dose limiting and thus optimal treatment of patients is not possible, as the chemotherapy needs to be stopped or reduced. Therfore patients cannot finish the course of chemotherapy and run a higher risk of relapse or recurrence of their cancer. Since years science searches for compounds to protect the nerve function, in order to enable patients suffering from MM to proceed being treated with chemotherapy.

Therefore it is highly important to point out that recently a natural occuring compound palmitoylethanolamide (PEA) has been identified in a clinical trial in MM patients, which indeed counteracts the side-effects of chemotherapy in blood cancer and restores nerve functions.

Italian neurologists from the neurological department of professor Cruccu, of the university of Rome, assessed the effect of PEA on pain and nerve function in patients with chemotherapy-induced painful neuropathy. 

Welcome to our Institute for neuropathy and neuropathic pain, and our Website. We gathered here for you many articles in the field of neuropathy and neuropathic pain. In our centre we are specialised in treating patients suffering from neuropathic pain and neuropathy following an Integrated Medicine concept. Part of our activities are within the field of consultation. We assist pharmaceutical companies in R&D strategies related to finding new drugs to treat neuropathic pain and neuropathy. 

In our institute we have a 100% focus on treating patients suffering from neuropathy and neuropathic pain. 

Palmitoylethanolamide ('PEA') is a endogenous compound and is in Europe available for the treatment of chronic pain and chronic inflammation. Most clinical data have been gathered and published around its efficacy in various neuropathic painstates, such as in diabetes, carpal tunnel syndrome, sciatic pain, and we outline these indications and the clinical and preclinical data below. 

Under the follow link an extensive review for specialists can be downloaded. The article appeared in The Open Pain Journal (2012) 

Palmitoylethanolamide has be described as an endogenous fatty acid amide, belonging to the class of lipid signaling molecules (autocoids). Since 50 years of research around this molecule, the last decade the number of scientific papers on PEA's biological and clinical activity has been expanded to nearly 400.

PEA has been demonstrated to bind to a receptor in the cell-nucleus (a nuclear receptor, PPAR), a number of other receptors, and therefore it exerts a great varity of biological functions related to chronic pain and inflammation. It is considered as a breakthourgh in the treament of chonic pain, and with PEA a new mechanism of action in the world of analgesics has been introduced and validated in a great number of studies.

PEA can be seen as a glia modulator and proof of principle (POP) as well as proof of concept (POC) has been generated via PEA studies of glia as an important factor in the genesis of neuropathic pain.

Brandnames of drugs containing PEA 

PEA is available under various brandnames: Normast and Pelvilen in Italy and Spain, and as PeaPure (JP Russell Science Ltd) for the rest or the world. PeaPure is available in Europe as a food supplement. 

In Normast and Pelvilen, the active ingredient is palmitoylethanolamide. In Normast and Pelvilen excipients like magnesium stearate, povidone and polisorbate are added. In the Normast sachets a sweetener has been added, sorbitol.

In PeaPure the sole content is palmitoylethanolamide (no excipients). 

What exactly is Normast  and PeaPure?

In this page many clinical and patient driven questions will be discussed. This page is under construction. A website has been created for palmitoylethanolamide related science only.

Normast and PeaPure are brandnames for supplements containing a body own molecule, palmitoylethanolamide, against pain and inflammation.  

Normast however contains magnesium stearate, a alien fat for our body, undigestable and an excipient doctors recommend to avoid.

All scientific information is discussed in this review.

Why the supplement PEA (Normast, PeaPure) in chronic painstates? Is Evidence-Based Medicine Patient-Centered and Is Patient-Centered Care Evidence-Based? The patient should be the ultimate judge. Therfore Dr Painless points out that treating patients suffering chronic pain with the non-prescription drug Normast makes sense. Evidence-based medicine is a rather young concept that entered the scientific literature in the early 1990s.

It has basically a positivistic, biomedical perspective. Its focus is on offering clinicians the best available evidence about the most adequate treatment for their patients, considering medicine merely as a cognitive-rational enterprise. In this approach the uniqueness of patients, their individual needs and preferences, and their emotional status are easily neglected as relevant factors in decision-making. 

In our clinic we developed a new treatment protocol for pains in CRPS, Sudeck's dystrophic pains. We combine various treatments, all with a low propensity for side-effects. Basically our treatment protocol consists of:

1. Topical analgesic creams:

a. start with ketamine 10% racemic cream and on top of it (if necessary) DMSO 50% cream. 

b. or switch to amitriptyline 10% cream ( with/without DMSP 50%)

c. switch to Algonerv cream on top of either one of the creams before (consisting of the immune-modulator adelmidrol and capsaicine low concentration)

Creams in addition to:

2. Normast (palmitoylethanolamide) 600 mg twice daily.

Start with 20-30 days on Normast powder sublingually (melt in saliva under tongue, not to swallow, but to resorp in the mounth, and after treat with Normast 600 mg tablets twice daily. (order by www.ergomax.nl)

Topical creams in CRPS: background 

Chronic severe pain in Sudeck or CRPS we treat with a combination of various topical creams, especially a 10% ketamine cream, in severe cases together with DMSO 50% cream. Topical analgesics have clearly advantages over systemically administered medications. This is especially true for racemic ketamine. The reduction or elimination of side-effects is one of the major advantages.

Many patients are totally unable to ingest ketamine, but as a cream the application of ketamine is no problem. We treated already 40 patients without any problems, and a Canadian academic group decribed another group of 60 patients. Topical analgesics differ from transdermal delivery methods in that prescribers use topical applications to deliver local, rather than systemic effects.

In our institute we have developed a variety of special-compounded creams to improve our patients’ experience with intractable pain due to Sudeck / CRPS. Ketamine 10% is one example.We also developed amitriptyline cream, baclofen cream and gabapentine creams. 

Our compounded ketamine 10% cream can be used for specific patients in e.g. the Netherlands, Germany and the UK if the physicians order a prescription document at

Treating neuropathic pain has to follow a multimodel painrelief approach. here we quote some lines from an FDA document concering pain treatment. An approach to improving pain control that addresses concerns with adverse events is to make use of a combination of different analgesics. By combining drugs lower doses can of each individual analgesics can be prescribed. In addition to the potential safety benefits of combination therapy, other potential advantages to use of a combination of analgesic drugs include the potential to overcome tolerance, improve efficacy, and decrease time- to-onset limitations of monotherapy.

How to best treat the elderly and frail patients suffering from neuropathic pain? For painphysicians this is a key question. Happily new data are guiding our prescribing behaviour in this field. The most important issue is how to achieve optimal analgesic efficacy without creating bothersome side effects like dizziness and unsteadiness or unwanted drug interactons! For instance, the best analgesics, the TCAs in elderly can cause cognitive functiondisturbances, confusion, gait disturbances, and falls. 

The famous Dutch surgeon Noordenbos wrote in 1959: "One-one synaptic transmission must be the exception rather than the rule in the nervous system. Any nerve cell located in the anterior horn. . . could hardly be expected to synapse at higher level with one such similar cell only. It will probably send ramifications to many other locations, and in turn be acted upon by the ramifications of many other cells. . . Far from being a continuous chain of short neurons, these fibres must constitute links in an extremely complicated nerve net in which, within limits, everything synapses more or less with everything else." It is clear that half a century later our therapy of pain is based on these deep insights of Noordenbos, and multimodal therapy is now the hallmark of how to treat neuropathic pain. This is because it is difficult to treat neuropathic pain with one drug only. In our centre we nearly always prescribe two or more oral drugs and mostly also topical creams and supplements together to get the patients out of the red zone of discomfort.

Heavy neuralgia radiating to the leg is also called sciatica or lumbosacral radiculopathy. Doctors have called this neuritis or neuritis of the sciatic nerve, the Nervus Ischiadicus, for a long time. This old concept has now been given a complete new turn.

Sciatica is caused by mechanic pressure by an intervertebral disc on the beginning of the sciatic nerve, the so-called nerve root within or just outside the vertebral column. Because of that pressure the nerve becomes inflamed and then the pain starts usually quite sudden. Then an inflammation that is maintained by the pressure on that nerve, the hernia, starts. 

Palmitoylethanolamide: in 2012 more than 300 entries in pubmed for this interesting molecule!

The internationalizarion of PEA started at the Third International Congress on Neuropathic Pain, Athens, Greece, May 27 – 30, 2010.

A. Biasiotta, S. et al presented a poster which demonstrated a clinical relevant and electrophysiological measurable effect from this rather unknown compound classified as medical food, palmitoylethanolamide. The compound is available as dietfood for medical purposes (brandname Normast) in various European contries and under the brandname PeaPure (a supplement) via the internet.

This is very interesting for doctors as well as patients, as PEA is an endogenious fatty acid without any troublesome side-effects and easy to use to reduce pain, even together with other drugs.

Lipids like N-palmitoylethanolamine can act as signaling molecules, activating intracellular and membrane-associated receptors to regulate physiological functions. The signaling lipid PEA is known to activate intracellular, nuclear and membrane-associated receptors and regulate many physiological functions related to the inflammatory cascade, and thus is of high interest in the treatment of neuropathic, or gliopathic pain.

Normast e PeaPure: informazioni palmitoilethanolamide:PEA è disponibile come PeaPure, Normast, Pelvilen e attraverso gli altri nomi commerciali. Normast in Italia attraverso la farmacia e ottenere PeaPure è realizzato nei Paesi Bassi e in tutto il mondo come un supplemento inviato.

I neutraceutici PeaPure® e Normast®, sia palmitoiletanolamide antidolorifico naturale (PEA) contengono, aprendo la strada a un nuovo metodo naturale di trattamento del dolore cronico. Entrambi i prodotti sono realizzati secondo i più alti standard (GMP). Perché PEA nei Paesi Bassi solo dal 2010, e abbiamo anche molte domande per telefono, ecco un elenco di domande e risposte. Anche domande e commenti da parte di persone su Fori di discussione su PEA parlare, abbiamo elaborato.

Fine anno del 2012 nei Paesi Bassi, sono decine di migliaia di pazienti trattati con PEA. Non ci sono effetti collaterali significativi segnalati. PEA può essere senza problemi, oltre a prendere altri farmaci e medicinali.

Nel 2012 un preparato palmitoiletanolamide nuovo introdotto. PeaPure contiene il più alto contenuto di PEA (vedi tabella). Solo PeaPure un certificato di analisi disponibili su Internet.

Thalamic pain after stroke is one of the most difficult to treat central painsyndromes. New therapeutic inroads are clearly needed, as the classical anti-neuropathic analgesics are not effective. In the future times we will need anti-gliopathic analgesics, as we pointed out elswere in our website.

The thalamus is a part of the brain were many mast cells reside. Mast cells play an important role in neuropathic pain. Palmitoylethanolamide (PEA) is a body-own fatty acid, synthetized in all our membranes, with mast cell stabilizing properties. PEA is registered in the catagory of medical food in Europe, and especially due to absence of side effects might be a promising new therapy for central thalamic pain. 

Carpal Tunnel Syndrome (CTS) is the most common compression neuropathy. It is the reason for pain and functional impairment. On the picture we see in yellow the median nerve, being compressed under a ligament in the wrist. This gives rise to chronic pain. Pain normally can be reduced with oral neuropathic analgesics. However, the side effects of most of the NSAIDS limit its use.  

Palmitoylethanolamide (PEA), a fatty acid occuring naturally in our body, has also neuropathic pain reducing properties. Furthermore, it stabilizes mast cells, present in the carpal tunnel. Besides the pain reducing effect, PEA has also neuroprotective properties. To evaluate the clinical effects of PEA in CTS, Italian researchers randomised 28 diabetic patients with CTS, in two groups: one group received PEA twice daily 600mg and the other group received placebo.

Treatment resistent abdominal pain, with unknown etiology can sometimes be treated succesfully by Cannabis. It might be that this chronic pain syndrome has something to do with small fiber neuropathy in the innervation network around the gut. But, whatever its etiology, it is merely a hypothesis and very difficult to substantiate. However, having said that, there are patients suffering from for instance diabetic neuropthy, with severe gasterointestinal complaits, and we feel these pains and complaints can be due to small fiber neuropthy. As Cannabis appeared to be a useful drug for treating treatment resistant neuropathic pain, we sometimes prescribe Cannabis to patients suffering from treatment resistent abdominal pain, and we follow the so called ex juvantibus approach. This means we give the patient the befifit of the doubt, that the pain might be caused by an internal neuropathy, and if so, whether the patients responds favourable on a treatment regime withn Cannabis, orally taken.  

In the journal JAMA, October 2009, was a description of a patient with diabetes mellitus and much discomfort from neuropathy. The doctor described the case, showed a list of drugs to see the usefulness of these values. Here on this table we see a number of recent rfindings and the relative strength of various painkillers for neuropathic pain. In this paper a clear message: Lyrica and Cymbalta are no better than older and cheaper drugs, which may be even better!

In the European Journal of Pain Supplements, 19 juli 2010 Garcia–Larrea discussed the value of Motor cortex stimulation (MCS), a relatively recent neurosurgical technique for pain control, in the treatment fo neuropathic pain. This is an abstract of a talk he gave at the  Third International Congress on Neuropathic Pain in Athens earlier this year. We were there and would like to make some commets, as this talk was discussed in great detail by a MD from the UK. She stated that there has not been conducted one methodological acceptable clinical trial analysing the safety and efficacy of this technique.

Natalizumab, a humanized monoclonal antibody against the 4 integrin did not help in treating a patient suffering from chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Although experimental evidence in an animal model pointed out that targeting 4 integrins in the inflamed peripheral nervous system may have clinical relevant effects, this was not the case in a patient.

At the Third International Congress on Neuropathic Pain, Athens, Greece, May 27 – 30, 2010 A. Biasiotta, S. et al presented a poster which demonstrated a clinical relevant and electrophysiological measurable effect from a rather unknown compound, in some European countries registered as food for medical purposes, a body own molecule, palmitoylethanolamide (PEA, Normast© or PeaPure©).

Patients suffering from small fibre neuropathy sometimes also suffer from difficult to treat low bloodpressure. In the Orient there is a registered drug for this dindication: L-DOPS (L-threo-dihydroxyphenylserine; Droxidopa; SM-5688). Droxidopa is a synthetic amino acid precursor which acts as a prodrug to the neurotransmitters norepinephrine (noradrenaline) and epinephrine (adrenaline). Unlike norepinephrine and epinephrine themselves, L-DOPS is capable of crossing the protective blood-brain barrier (BBB).

On 24 July 2008 the Committee for Medicinal Products for Human Use (CHMP) in Europe adopted a positive opinion, recommending to grant a marketing authorisation for the medicinal product Duloxetine  produced by Boehringer Ingelheim in capsules of 20 mg, 30 mg, 40 mg and 60 mg. The indications are: 

Until recently, regional anesthesia provided for the patient with a preexisting neuropathy has received scant attention. A review of major reference works dedicated to regional anesthesia spanning 87 years, and more than 4,700 total pages, found only 5 pages wherein the issue of central neuraxial anesthesia or PNB was discussed in the context of neuropathy. 

You are definitely familiar with symptoms as numbing, tingling, or prickling sensatiob,  after you have hit your funny bone, or your foot falls asleep. But for cancer patients, these sensations can be symptoms of either cancer itself, or, more often, a serious side effect of cancer therapy called neuropathy (injury to the nerves).

Combining Opioid and Nonopioid Activity in One Centrally Acting Oral Analgesic, is the communication of this newly registered opioid from the laboratories of Gruenenhal in Germany. The second wave of marketing communication is:  

1. MU-OPIOID AGONIST, and
2. ASCENDING PATHWAYS Works primarily on ascending pathways to inhibit transmission of pain impulses through binding to mu-opioid receptors, and
3. NOREPINEPHRINE REUPTAKE INHIBITOR DESCENDING PATHWAYS Works primarily on descending pathways to enhance the inhibition of pain signaling through norepinephrine reuptake inhibition. 

In April 2010 a new guideline was issued on the treatment of chronic pain: Practice Guidelines for Chronic Pain Management: An Updated Report by the American Society of Anesthesiologists Task Force on Chronic Pain Management and the American Society of Regional Anesthesia and Pain Medicine. 

In this guideline anesthesiologists of name and fame gathered and analysed all approaches to chronic pain. For acupuncture their assessment was:  

Surfing the net you may encounter many different treatments for neuropathy, and the anodyne therapy is one of those. In the internet you may find advertorials like the following: f you suffer from diabetic neuropathy, you may benefit from Anodyne Therapy--a non-invasive treatment that increases circulation and reduces the pain associated with peripheral neuropathy. The Anodyne Therapy System® helps to release nitric oxide from the red blood cells of patients suffering from diabetes. It does this with monochromatic infrared energy (MIRE) administered through flexible pads containing infrared diodes.