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.
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).
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.
Why the supplement PEA ( 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 een PEA-houdend product 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.
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.
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.
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.
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 een PEA-houdend product 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. een PEA-houdend product (palmitoylethanolamide) 600 mg twice daily.
Start with 20-30 days on een PEA-houdend product powder sublingually (melt in saliva under tongue, not to swallow, but to resorp in the mounth, and after treat with een PEA-houdend product 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
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.
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.
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 (‘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: een PEA-houdend product and een PEA-houdend product 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 een PEA-houdend product and the active ingredient is palmitoylethanolamide. In een PEA-houdend product and een PEA-houdend product excipients like magnesium stearate, povidone and polisorbate are added. In the een PEA-houdend product sachets a sweetener has been added, sorbitol.
In PeaPure the sole content is palmitoylethanolamide (no excipients).
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.
The link here under contains a nice and crisp talk by Dr Nadine Attal. She is a neurologist and pain specialist, Director of the Pain Evaluation and Treatment Centre of Hôpital Ambroise Paré, France, and a member of the INSERM U 792 team. Dr Attal is a member of several scientific societies, including the Society for Neuroscience, the International Association for the Study of Pain and the American Pain Society. Dr Attal has authored 60 referenced journal articles and over 30 book chapters, has co-ordinated books on neuropathic pain in France, and is associate editor for the journal Pain. She recently co-chaired the European Federation of Neurological Societies (EFNS) guidelines on the pharmacological treatment of neuropathic pain and was involved in the EFNS guidelines on the assessment of neuropathic pain. She also recently joined the NeuroPsig management committee.
een PEA-houdend product e PeaPure: informazioni palmitoilethanolamide:PEA è disponibile come PeaPure, een PEA-houdend product e attraverso gli altri nomi commerciali. een PEA-houdend product 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 een PEA-houdend product®, 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.
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 ( PeaPure).
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.
Treatment of refractory neuropathic pain is a clinical challenge. However, many new case reports and small clinical trials suggest that the N-methyl-D-aspartic acid (NMDA) receptor antagonists ketamine may be clinically useful in treating cases of neuropathic pain. Here a case report. This case report supports the idea that ketamine can be useful in the reduction of refractory chronic neuropathic pain and that the effect of ketamine can persist for many weeks after treatment.
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. een PEA-houdend product contains PEA too, but around 60%; Pevliven contains between 60-40% PEA.
Dr Gatti and colleagues from the medical department oif the university of Rome (Italy) (Dipartimento di Medicina
Critica, del Dolore e delle Scienze Anestesiologiche,
Università degli Studi di Roma, Viale Oxford, 81,
00100 Roma, Italy) described the efficacy and safety of palmitoylethanolamide (PEA) in 610 patients suffering from treatment refractory pains. Titel of the 2012 article was: Palmitoylethanolamide in the Treatment
of Chronic Pain Caused by
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.
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, een PEA-houdend product© or PeaPure©).
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.
Bupropion for the treatment of neuropathic pain. A short review.
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 een PEA-houdend product) 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.
The mechanisms relating to the development of post herpetic neuralgia (PHN) or zoster pain remain uncertain and many different factors are involved.
PeaPure: we will discuss some differences and similarities of these three nutraceuticals. Palmitoylethanolamide is the active ingredient in all three. een PEA-houdend product is the Italian branded nutraceutical, available in Italy probably since 2007. een PEA-houdend product was developed since the end of last year, and the name een PEA-houdend product refers to the normalization of mast cell hyperactvity. The brandname een PEA-houdend product has been created in 2005.
een PEA-houdend product is the brand name of the in Italy produced palmitoylethanolamide version, een PEA-houdend product 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.
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.