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 […]
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.
Under the titel ’Occipital Neuralgia Responding to Palmitoylethanolamide’ Rocco Salvatore Calabrò and Placido Bramanti reported a case in ‘Headache’, a female patient affected by occiptal-treatment-refractory-neuralgia that greatly improved after oral intake of palmitoylethanolamide (PEA).
PRECISION TM Spinal Cord Stimulator (SCS) System : clinical studies forming the base of the registration of this device. Here a summary of the various studies supporting the registration of the precision spinal stimulator.
One of the recent insights regarding the workingmechanism of PEA (palmitoylethanolamide) is that this molecule influences PPAR-alpha. PPAR-apha is a receptor located in the nucleus of the cel with a long name: peroxisome proliferator-activatedreceptor alpha. PEA is available in its purest form as PeaPure. PeaPure contains PEA only. Normast contains PEA too, but around 60%; Pevliven contains between 60-40% PEA.
Trigeminus neuralgia is difficult to treat. For those patients were medication such as carbamazepin is not helpful, the neurosurgeon can treat with the so called Gamma Knife….
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.
Complex regional pain syndrome (CRPS) is a chronic pain condition most often affecting one of the limbs (arms, legs, hands, or feet), usually after an injury or trauma to that limb. Surgical sympathectomy has long been seen as a realistic option to treat CRPS. The use of this operation that destroys some of the nerves however has always remain controversial. In a recent Cochrane analysis no evidence could be found. The conclusion was:
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.
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.
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).
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.
Cannabis treatment for meuropathic pain using low dose cannabis during prolonged periods of time due to slow resorption from butter rich cannabis cookies: a better way to administer cannabis than the classical joint or marihuana tea.
Bupropion for the treatment of neuropathic pain. A short review.
The mechanisms relating to the development of post herpetic neuralgia (PHN) or zoster pain remain uncertain and many different factors are involved.
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.
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
More and more randomized, double-blind, placebo-controlled trials on neuropathic pain treatment are published, and it seems there is a surge! Will this help the patient? Some top pain experts analysed one hundred and seventy-four studies, a twothird increase in published randomised, placebo-controlled trials in the last 5 years. What did they find out?
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:
- MU-OPIOID AGONIST, and
- ASCENDING PATHWAYS Works primarily on ascending pathways to inhibit transmission of pain impulses through binding to mu-opioid receptors, and
- NOREPINEPHRINE REUPTAKE INHIBITOR DESCENDING PATHWAYS Works primarily on descending pathways to enhance the inhibition of pain signaling through norepinephrine reuptake inhibition.
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.
Low dose naltrexone is popular in the alternative treatment world. It is a bit strange, as this molecule is quite non-alternative. But low dose naltrexone (LDN) is recommended on lay internetsites for a multitude of diseases, from MS to cancer. That always provokes anti-bodies by doctors, but naltrexone indeed has anti-inflammatory properties. It might be an interesting treatment option for treatment refractory neuropathic pain patients.
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).
Research over the last few decades has shown an increased use of complementary and alternative therapies (CAM) and an integration of aspects of CAM into mainstream medical treatment, health care organisations and insurance plans. It has been shown that the process of care may be as important as the outcomes of treatment, which may explain in part the relatively large popularity of CAM for many patients on a world wide base. (Muir Gray JA. Evidence-Based Healthcare. How to Make Health Policy and Management Decisions. 2. London: Churchill Livingstone; 2001)
In a head to head comparison study the Italian research group from the Department of Orthodontics, of the School of Dentistry, at the University of Bologna, could demonstrate that treatment with the natural analgesic compound palmitoylethalonamide (available under the brandnames Normast® or PeaPure® ) was superior over the treatment with a classical NSAID in temporomandibular joint disorder (TMJD), or Costen syndrome.
The EMEA has adviced against the marketing authorization of Lyrica® in the indication fibromyalgia in Europe. This is their argumentation: