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In this section English articles are published on neuropathy.

The Relationship Between Peripheral Neuropathy and Diabetic Retinopathy

There is a clear relationship Between Peripheral Neuropathy and Diabetic Retinopathy, both are based on the the same pathogenesis. At the the World Ophthalmology Congress (WOC) 2010, June 7 the following data on the relationship were presented as a poster:

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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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CIAP and Palmitoylethanolamide (PEA) for neuropathic pain

pea.jpg We present a case of a 90-year old woman, born in 1920, suffering since years from axonal idiopathic neuropathy and neuropathic pain. Pain scored 7-9 on a 11-points Likert scale when I first saw her. Walking increased burining pain to a score of 9, and during resting the score was 7. On the DN-4 scale she scored 6, which is indicative for neuropathic pain. 

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KU-32 in diabetic neuropathy

KU-32 showed promessing effects in a mice model. KU-32 inhibits a specific member of a family of proteins, the socalled molecular chaperones. Diabetic mice were administered KU-32. The compound effectively stopped diabetic polyneuropathy and could even restore the sensory neuron functions of the damaged nerve tissue. 

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Ibudilast, XT101 in neuropathic pain

The glial blocker XT101 demonstrated in the preclinical phase to be able to upregulates IL-10. It is developed by Xalud Therapeutics, Inc. Data on AV411 (ibudilast) has been presented by Paul Rolan, M.D., FRACP, Professor of Pharmacology, University of Adelaide, Australia, at the 10th International Conference on the Mechanisms and Treatment of Neuropathic Pain held in Salt Lake City, Utah, in 2007.

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Rise of a concept: neuropathic pain

Medical terminology seems stable. However, although terms and words seem not to change, the content of the concepts might be quite different in different periods of time. This is exactly the case with the concept ‘neuropathy’. In the nineteeth century for instantce its meaning referred to all diseases of the nervous system, including psychiatric disorders. In order to analyse the emergence of the concept ‘neuropathic pain’, as well as the change in its definitions, we analysed a number of publications since this concept was launched. Related concepts, such as neuralgia, neuritis and neuropathy will be discussed too.

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Depression: a gliopathic disorder?

Antidepressants in our culture: an expanding wave. Although scientific studies do not support the use of antidepressants in mild to moderate depression, prescriptions for anti-depressants are soaring high. We want to share to contemporary critics on our use of anti-depressants. The first is dr. Helen Fischer, a well known antropologist from the VS. She warns for chronic use with seronin-uptake inhibitors. By increasing the serotonin in the brain during months to years, other neurotransmittersystems tend to collaps, such as the dopaminergic system. And, as she vividly points out, the dopamine system is key for a healthy love life and for the kick in life. The second scientist is dr. Vladimir Maletic, who recently argued depression is not a nerve cell disorder, but a glia cell disorder, a gliopathic pathology, just as neuropathic pain is!

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Pharmacologic Treatment of Central Post-Stroke Pain

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

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Hacking into chronic painstates with the endocannabinoid palmitoylethanolamide

Palmitoylethanolamide (brandnames een PEA-houdend product and PeaPure) is now registered as a supplement in various European countries and is one of the major existing new non-ionchannel tools to target the glia and the neurons in neuropathic and chronic pain. The availability of this compound leads to this discussion on how to influence chronic pain states with this endocannabinoid.

Chronic pain can disrupt brain function and cause many somatic and psychological problems. When neurons fire too much they may change their connections with other neurons and may even die. Crucial to understanding chronic pain are insights in the function of neuronal networks and the role of the all-invading glia cells. But: ‘Glia are nervous system caretakers whose nurturing can go too far. 

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Neuronal damage leads to increase production palmitoylethanolamide and other endocannabinoids

Neuronal damage as assessed by transection of long-range projections apparently provides a strong time-dependent and area-confined signal for de novo synthesis of various endocannabinoids, presumably to restrict neuronal damage. In an elegant study Sonja Kallendrusch and colleagues pointed out some recent studies demonstrating the neuroprotective properties of endocannabinoids in various models of neuronal lesion in vitro and in vivo. Palmitoylethanolamide, they emphesised, mediates its neuroprotective effects via dual PPAR alpha activation on microglial cells and neurons.

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PeaPure: some differences and similarities

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.


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Johnson & Johnson work on glutamate as a target for neuropathic pain

Johnson & Johnson work on glutamate as a target for neuropathic pain and in 2009 researchers from Belgium published their understanding about the role of the glutamate receptor in neuropathic hypersensitivity.

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AM1241, a Canabinoid ligand against cancer pain

Cannabis is an age-old analgesic which we use off and on for the treatment of severe neuropathic pain, as an adjunct to other treatment modalities. Now, a new study demonstrates the putative positive effect of  a new Cannabinoid CB(2) agonists , AM1241.

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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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Neuropathic pain: what is it?

Neuropathic pain is defined as “Pain initiated or caused by a primary lesion or dysfunction in the nervous system”. Neuropathic pains are divided into peripheral neuropathic pain due to lesion of the peripheral nervous system and central pain following lesions of the central nervous system.

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ALGRX 4975 (Johns Hopkins University)

ALGRX 4975 (Johns Hopkins University) is under development in neuropathic pain, in phase II.

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Burning feet and neuropathy

In neuropathy and neuropathic pain patients can be suffering much from burning feet. Whatever the try, the burning and stinging sensations do not waver. The bruning sensations, the sensations of hot and painful feet  is due to damage to the nerves, in this case the long nerves from your spinal cord to your feet. In some cases, the burning feet may be so painful that you cannot sleep anymore.

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Annual Cost of diabetic neuropathy: circa $4000

The health care costs associated diabetic polyneuropathy in patients range from $1,600 to $7,000 per case each year. As the incidence of neuropathy is expected to rise as the result of an increasing older population at elevated risk diabetes, the overall costs will rise. Here a press release on the costs for neuropathy, dated 27 April 2010, released by the American Pain Society.

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MDA19: pharmacological profile of cannabinoid ligand

The cannabinoid receptor 2 (CB(2)) agonists are potential therapeutic targets in the treatment of neuropathic pain. The pharmacological profile of  N’-[(3Z)-1-(1-hexyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]benzohydrazide (MDA19), a CB(2) agonist suggest MDA19 could be a analgesic for the treatment of neuropathic pain.

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Nerve cell regeneration and the receptor called DCC (Deleted in Colorectal Carcinoma)

Researchers from the university of Montreal published in Cell an article that gives some new insight in the issue of nerve cell regeneration. "We found an alternate way that helps nerve cells respond quickly and locally," sayd one of the authors of the paper, Philippe P. Roux, a professor of pathology and cell biology and a researcher at the University of Montreal Institute for Research in Immunology and Cancer (IRIC). He sees new therapeutic targets in future based on this principle:  "We can envisage manipulating this alternate mechanism to make cells respond locally to their environment. Our findings mean that scientists must consider a new way that cells organize themselves to perform essential functions."

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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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MAG neuropathy

Here an entry from a patient’s blog with a description of a patient of what he experienced:

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What You Can’t Feel Can Hurt You

What You Can’t Feel Can Hurt You, the title of a crisp article on neuropathy and its consequences for our health. 

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Glia cells, abundant in the nervous system


Glia cells comprise 90% of the cells in the nervous system. The other 10% of cells consists of neurons. In the artist impression we see the high number of glia cells for each separate neuron.

The word ‘Glia’ is derived from the Greek word for "glue" giving the impression that the main function of these cells is to keep the brain from running out of our ears. (Bear M.F. Neuroscience, exploring the Brain 2007 3rd ed.)

Glia cells are thought to insulate, contribute and nourish neighbouring cells. Recently, more and more knowledge has been gained in the role of glia in neuropathic pain. Glia seems to play a much more important role than anticipated, hence the term ‘gliopathic pain’. Glial activation is required and sufficient for chronic pain sensitization, the root cause of neuropathic pain.

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CRPS type 1 and ketamine cream

crps-ketamine.jpg CRPS type 1 and ketamine cream:

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Pudendal neuralgia responding to a novel use of palmitoylethanolamide

Pudendal neuralgia is the most common and most disabling form of pelvic pain. It presents as unilateral or bilateral burning pain of the anterior or posterior perineum that is worse on sitting and relieved by standing, not usually associated with night pain.This pain is a cause of chronic, disabling, and often intractable perineal pain.

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Inflammatory bowel disease, mast cells and PEA

Neuroinflammation in inflammatory bowel disease, the titel of a leading article on the role of amongst others the mast cell in IBD. ( Journal of Neuroinflammation 2010, 7:37). We quote from this open access article several parts related to the impact of the mast cell on IBD. These quotations demonstrate that the use of the natural anti-inflammatory agent palmitoylethanolamide might be a very useful to treat patients suffering from these disorders.

In our clinic we saw a clear therapeutic effect when we prescribed PEA in a patient suffering from colitis ulcerosa combined with severe neuropathic pain. Not only was the neuropathic pain reduced in severeity by more than 50%, the same holds true for the symptoms of the IBD, diarrhoea and fecal incontinence.

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Ten year old paralysed King Charles spaniel runs again after palmitoylethanolamide!

een PEA-houdend product-spaniel.jpg Ten year old paralysed King Charles spaniel runs again after een PEA-houdend product! And no PSOM, no inflammed eyes anymore. Dose administered: 300 mg een PEA-houdend product granulate twice daily. 

After 6 months the dog was switched over to a new PEA product, PeaPure. The clinical reaction was even superior, probably due to the absence of pharmaceutical excipients. The dog walked better, longer and the mild eye inflammations under een PEA-houdend product treatment vanished totally and within 1 week. The now 11 year old dog is already 4 months stable on PeaPure, and nearly a year on PEA.  

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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 ( PeaPure).

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Multimodal pain management, and the role of palmitoylethanolamide

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. 

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