In the following sequence of presentations we bring to you the essence of knowledge around the body-own compound and supplement palmitoylethanolamide! We start with the general introduction, an overview of palmitoylethanolamide, an endogenous cellular protectant in plants, invertebrates, vertebrates and humans, tested extensively since 1970 and widely available as food supplement. Its main action is […]
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).
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:
Paclitaxel is an effective chemotherapeutic agent that is widely used for the treatment of several cancers, including breast and ovarium cancer. However, it induces disabling and potentially long-lasting sensory neuropathy.
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©).
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.
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.
Although pain is a prominent symptom in patients suffering from syringomyelia, and this central neuropathic pain is very difficult to treat. However, more than half of all patients with syringomyelia suffer from symptoms related to central neuropathic pain. In the video you can see one of our patients, suffering from syringomyelia telling his story and reporting the effect of our treatment of the neuropathic pain:
Numbers needed to treat in neuropathic pain are not very impressive. If you would tell your patient, I have to treat at least 5 patients like you in order to help one of those patients reach a pain reduction of 50%..imagine how many patients would frown and say…excuse me? (if they are British that is..). Because patients frequently fail to receive adequate pain relief from, or are intolerant of, first-line therapies prescribed for neuropathic pain, the opening sentence of a new (2011) article on refractory neuropathic pain, ‘Pregabalin, the lidocaine plaster and duloxetine in patients with refractory neuropathic pain: a systematic review’ by Melanie Plested and collegues, among which one works at Pfizer’s (interesting..!).
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, 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.
Topiramate is a drug we should not forget in treating patients suffering from neuropathic pain. Especially not for patients with refractory neuropathic pain, that is if other drugs do not help.
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.
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.
Gingivitis is not nice. Redness and pain of the gums and bad breath. The cause of gingivitis is an inflammation of the gingiva, or of the gums. It is found in well over 60% (!) of adults over age 45 or even nearly 100%, according to some dentists. Inflammation of the gums is usually the result of poor dental hygiene. Sadly enough it creates a second, more serious problem, periodontal disease. Unless corrected this usually poses a real thread for both tooth and jawbone. Mast cells can be found in normal gingivae as well as in acute necrotizing gingivitis, chronic marginal gingivitis,andand pregnancy gingivitis, and these cels have been identified already more than half a century ago.
The Indian group of Agrawal and collegues (2007) explored the analgesic effects of glyceryl trinitrate spray in neuropathic pain. They suggested that impaired nitric oxide (NO) synthesis may play an important role in the pathogenesis of painful diabetic neuropathy. Some studies demonstrated impaired neuronal nitric oxide generation in diabetic rats induces hyperalgesia and in other studies a decreased nitric oxide production was seen to to a reduction in endoneural blood ﬂow in type 2 diabetic patients with neuropathy. Both iso-sorbide dinitrate as well as glyceryl trinitrate may act as potent nitric oxide donor and have similar pharmacological activity compared to endothelial derived relaxing factor, a nitric oxide dependent enzyme with vasodilator capacity. In our institute we have now gathered quite some experience using isosorbide dinitrate cream in neuropathic pain, with good results.
As yet, no “gold standard” has emerged for multimodal pain management for neuropathic pain. The various multimodal pain protocols that have been developed, however, share similar objectives, to reduce side effects, to reduce dose and to avoid and even to eliminate narcotics leading to troublesome side-effects while reducing the quality of life. Because pain involves multiple mechanisms that rely on different receptor systems, it is beneficial to utilize a multimodal approach to achieve pain relief in complex pain states such as neuropathic pain.
Vitamin E protects against nerve damage from chemotherapy, showed by French researchers, in a study of more than 100 patients, a study published in 2010.
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.
Amitriptyline as good as pregabalin for painful diabetic neuropathy says a review ariticle on Diabetes in control.com, dated March 23, 2010. This is based on the results of a head to head comparison of both drugs in a group of 41 patients. The study had some methodological flaws, but the results are in line with our expectations and experiences. Both drugs have similar efficacy, but amitriptyline, if dosed higher up (>25 mg an) has more side- effects.
Palmitoylethanolamin (Normast®;PeaPure®) is a endogenous lipid with analgesic and anti-inflammatory properties. In a study were 30 patients were entered, suffering from diabetic neuropathic pain and post-herpetic pain, palmitoylethanolamide was combined with pregabalin in the treatment of neuropathic pain.
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.
Vitamin D could save the country about €37.5 billion in health care costs, according to a new review of professor A. Zittermann.
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.
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.
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.
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.
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:
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
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
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.