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Treatment

Several treatment modalities are available within the field of neuropathic pain and neuropathy.

Palmitoylethanolamide, PEA: key items presented

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 […]

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Natalizumab in chronic inflammatory demyelinating polyneuropathy (CIDP)

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.

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Occipital Neuralgia Responding to Palmitoylethanolamide

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).

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PRECISION TM Spinal Cord Stimulator (SCS) System

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.

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PEA influences PPAR

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.

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Trigeminus neuralgia treated with Gamma Knife surgery

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…. 

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Normast and PeaPure: questions and answers

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.

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Motor cortex stimulation (MCS) for neuropathic pain

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.

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Cervico-thoracic or lumbar sympathectomy for neuropathic pain and complex regional pain syndrome

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:

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Combination of analgesics in neuropathic pain

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.

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Carpal tunnel syndrome treated with PEA

median_nerve_in_ct.gifCarpal 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.

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Neuropathic low blood pressure: Droxidopa

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).

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Evidence based medicine, patient centered medicine and the place of PEA

ebm.jpg 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. 

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Cannabis cookies for neuropathic pain

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.

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Bupropion for the treatment of neuropathic pain.

Bupropion for the treatment of neuropathic pain. A short review.

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Zoster pain and vitamine D?

The mechanisms relating to the development of post herpetic neuralgia (PHN) or zoster pain remain uncertain and many different factors are involved. 

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Anodyne Therapy System® for neuropathy: not proven!

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. 

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Treatment of CRPS pain acc to protocol including ketamine (&DMSO) creams

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 infoneuropathie.nu.gif

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New treatment options neuropathic pain urgently needed

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?

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NUCYNTA® a new opioid from Gruententhal

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. 

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Treatment of neuropathic pain in elderly and frail patients

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. 

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Low dose naltrexone for neuropathic pain

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.

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Palmitoylethanolamide (PEA): information for MD’s

pea.jpeg

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). 

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Integrated Medicine concept for the treatment of neuropathic pain

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) 

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Palmitoylethanolamide (PEA) versus NSAID in the treatment of TMJD pain

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.

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Pregabalin, Lyrica® not for fibromyalgia in Europe

The EMEA has adviced against the marketing authorization of Lyrica® in the indication fibromyalgia in Europe. This is their argumentation:

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Integrated Medicine concept for neuropathic pain at the Berlin congress (2010)

Treatment of neuropathic pain, an overview presented at the 3rd European Congress for Integrative Medicine,in Berlin, December 3rd, 2010. The founding fathers of the Institute of Neuropathic pain attended the above mentioned congress to present the integrated treatment concept for neuropathic pain to an audience of physicians interested in pain treatment. The director of research and development from the institute, professor Jan M. Keppel Hesselink, presented the multimodal therapy as it has been developed within the institute for the past years.

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Neuropathic pain treatment as presented by Dr Nadine Attal

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.

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Intractable neuropathic pain in Diabetes treated with palmitoylethanolamide and topical cream

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).

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Pharmacotherapy of painful neuropathy

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!

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