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MS spasms and pain treatment with body’s own substance palmitoylethanolamide

Palmitoylethanolamide is a new and promising treatment against pain and inflammation. It’s available as a supplement without prescription. PeaPure is a supplement in its purest form.

Patients that suffer form MS pains and spasms can get some relief from this substance. In Italy, many neurologists are using this substance and both patients as neurologist are positive about it. For example, during a recent congress the results of 20 patients were discussed, of which the majority experienced a clear decrease of pain, as is shown in the table. The higher the bar, the stronger the pain. You can also see that out of the 20 patients, some did not notice an effect.

Pain and spasms ruin the lives of quite a few people with MS. Spasms are a major problem in MS and the medicines available are not always very effective, or have nasty side effects. The spasms can be very painful, as well as interrupt movement. Many MS patients also experience neuropathic pain, burning pain in legs or other body parts, that aren’t always easy to treat with neuropathic painkillers like gabapentine and pregabaline (Lycrica®).


Pain, spasms and painful spasms with MS

Neurologists in the Netherlands often prescribe baclofen or Valium for these types of complaints. These can help, but can also create drowsiness. That’s why it’s important to familiarize yourself with other treatments as well.

Several neurologists in Italy have given the pain-relieving and anti-inflammatory bodily substance palmitoylethanolamide to MS patients for spasms, painful spasms and neuropathic pain.


PEA, pain relief without drowsiness

Research shows that spasms due to MS can sometimes be treated successfully with cannabis. But not all patients want to use cannabis. The patients below were treated with palmitoylethanolamide, a fatty acid produced by the cells of our own bodies. This substance doesn’t cause drowsiness and doesn’t make you high or stoned.

Here we will summarize the treatments with PEA on these patients.


Burning legs, MS and bound to a wheelchair

A 37-year-old man with multiple sclerosis suffered from burning sensations in the legs. Treatment with a total of 300mg pregabaline wasn’t effective enough. After that he was treated with palmitoylethanolamide, which significantly improved the burning sensations as well as his interrupted sleep pattern.

A 55-year-old man with multiple sclerosis for 15 years had been bound to a wheel chair for 5 years. He experienced a lot of spasms, especially during the night. He was given a dose of 300mg of palmitoylethanolamide daily. After 10 days he noticed the spasms had decreased in intensity and frequency. After 15 days the spasms were nearly gone.


Ten MS patients with neuropathic pain

Another clinic accomplished the following results with a group of 10 MS patients who all experienced neuropathic pain and spasms.  Treatment of the spasms and neuropathic pain with gabapentine and pregabaline showed no results. Palmitoylethanolamide was added to this regime, which improved the symptoms noticeably.

Research among patients had indicated before that the so-called endocannabinoid system in MS patients functions differently than in healthy volunteers. Researchers were of the opinion that the cannabis-like molecules that are produced by our body (the endocannabinoids) can have a nerve protecting and immune modulating effect on MS:

Therapies that affect the endocannabinoid (EC) system may have immunomodulatory, symptomatic and neuroprotective effects. [1]


Mice with MS and palmitoylethanolamide

There is a so-called mice-model for MS that shows that palmitoylethanolamide both inhibits the inflammatory aspects that look like MS as well as improved paralysis. Here are a few observations from the study:

Increasing evidence from animal studies suggests that cannabinoids could also prove efficient to fight neurodegeneration, demyelination, inflammation and autoimmune processes occurring in this (MS) pathology.

However, the use of cannabinoids is limited by their psychoactive effects. In this context, potentiation of the endogenous cannabinoid signalling could represent a substitute to the use of exogenously administrated cannabinoid ligands.

Here, we studied the expression of different elements of the endocannabinoid system in a chronic model of MS in mice.

We first studied the expression of the two cannabinoid receptors, CB(1) and CB(2), as well as the putative intracellular cannabinoid receptor peroxisome proliferator-activated receptor-alpha. We observed an upregulation of CB(2), correlated to the production of proinflammatory cytokines, at 60 days after the onset of the MS model.

At this time, the levels of the endocannabinoid, 2-arachidonoylglycerol, and of the anti-inflammatory anandamide congener, palmithoylethanolamide, were enhanced, without changes in the levels of anandamide.

Finally, the exogenous administration of palmitoylethanolamide resulted in a reduction of motor disability in the animals subjected to this model of MS, accompanied by an anti-inflammatory effect. This study overall highlights the potential therapeutic effects of endocannabinoids in MS.[2]

What the authors are saying is that palmitoylethanolamide has a clear anti-inflammatory effect in this MS model.

Based on both of these studies it looks like with both the mice-model as well as with humans, the body utilizes palmitoylethanolamide as an attempt to heal itself. An increase in palmitoylethanolamide in the mice-model resulted in a decrease of inflammation and better mobility with the mice. So, paralysis decreases as well.

Keep in mind that a mice-model is not a human model and that the use of PeaPure doesn’t automatically mean that paralysis will decrease.


Pain, spasms and spasticity treated with palmitoylethanolamide

These short case studies show that there are MS patients with neuropathic pain, painful spasms and/or spasticity that benefit from treatment with the body’s own palmitoylethanolamide.

This pain relieving and anti-inflammatory substance is formed in our own cells and has been studied extensively on a wide range of conditions, including hernia pain, shingles pain, diabetes, carpal tunnel syndrome and jaw pain. All of these studies showed a good pain-relieving effect and had no problematic side effects.

Palmitoylethanolamide belongs to the group of endocannabinoids. These are substances that are similar to cannabis and produced by our own tissue (endo comes from endogenous, meaning from within).

Palmitoylethanolamide is available in the Netherlands as PeaPure. Unfortunately it is not reimbursed by insurance, as it is a supplement. The substance has a clear pain relieving and spasm-inhibiting effect, as is shown in the examples above, and doesn’t have any problematic side effects. On top of that, the substance can be combined with other medicine with out any negative interactions. Seniors can also safely take this supplement.


Palmitoylethanolamide: a non-drowsy pain relieving cannabinoid

Palmitoylethanolamide (PEA) is a pain reliever with an entirely new working mechanism. The substance is similar to cannabis, but without the psychoactive side effects. It’s a substance produced by our own bodies and, available in the Netherlands as the supplement PeaPure in 400mg capsules.

In the 60’s and 70’s PEA was available as Impulsin for flu prophylaxis, mainly in the Czech Republic. At the time, this indication was supported by three different positive studies. However due to lack of knowledge about the working mechanism, at that time they thought the substance worked through the lymphocytes, interest for this body’s own amide declined. This interest has been back on the rise since the 90’s and hundreds of pharmacological and a number of clinical studies have been done. Everything seems to indicate that we’re dealing with a promising pain relieving and anti-inflammatory substance, without negative side effects or notable interactions (no influence on other medicine like Baclofen, cortison, etc).

After the discovery of anandamide in 1992 and of cannabis receptors, the interest in PEA quickly increased. In the meantime, this molecule has been studied on different animal models for over half a century. These pre-clinical and clinical studies range from flu prophylaxis, multiple sclerosis, trauma to the spine and stroke, to inflammation and neuropathic pain.


PEA animal models for inflammation and pain

Half a century ago, PEA was studied as a boost for non-specific immunity by Czech researchers. [3][4]This resulted in clinical studies among children and adults to get an impression if PEA could help prevent flu, which indeed appeared to be the case. The substance was marketed as Implusin. [5][6][7]

With complex inflammation models, like multiple sclerosis and traumatic spine damage, PEA clearly shows to decrease the inflammation component and improve motor function. [2][9] In the latest model, PEA shoed to have a number of clear effects. PEA decreases:

  1. The inflammation response in the spine,
  2. The neutrophil cell infiltration,
  3. The production of nitrotyrosine,
  4. The expression of pro-inflammatory cytokines,
  5. The kappa-B activity
  6. The expression of nitrogen monoxide synthesis,
  7. The apoptosis

Anandamide and PEA are both synthesized from a communal precursor molecule and work synergistically. Animal models showed that the pain relieving effect of these two molecules is 100 times stronger when both substances are present. Gas chromatographic and mass spectrometric research showed that locally produced concentrations of both molecules is enough to locally stimulate cannabis receptors. [10] Through a large number of animal models for inflammatory pain and neuropathic pain PEA shows to have a consistent analgesic and anti-inflammatory effect. [11][12][13][14][15][16][17][18]


Clinical studies and examples

Never before have there been this many pre-clinical studies available about the medical effectiveness of a dietary supplement. They formed the foundation for the development and execution of a number of clinical studies of chronic pain indications and conditions in which chronic inflammation plays a part.

Here we will discuss the clinical results of PEA for hernia pain, pain due to carpal tunnel syndrome, diabetic neuropathic pain, pain due to temporomandibular dysfunction, postherpetic pain, pain due to endometriosis and pain in the pelvis.

The largest study performed on PEA was among patients with severe hernia pain. The study was published in a Spanish medical journal in 2010. In a double blinded, randomized study more than 600 people with hernia were treated with PEA or a placebo. The dose of PEA was 600mg twice a day for 3 weeks. The study was conducted in 9 hospitals and university centers in Italy. The patients that were treated with PEA clearly and significantly showed a higher pain relieve than the placebo. [19]

A second study researched the effects of PEA on 20 patients with diabetic neuropathic pain, using a dose of 600mg PEA per day. On top of taking pain scores and measuring neuropathic symptoms they compared conduction speed before and after treatment. Both the pain as well as the neuropathic symptoms improved significantly. Furthermore, the neurophysiological parameters turned out to have somewhat improved, however not significantly. [20]

A third comparative study treated pain due to carpal tunnel syndrome with PEA and was evaluated after 4 as well as 8 weeks. After 4 weeks there were significant differences already and these effects increased after 8 weeks. The function of the hand improved with the treatment of PEA, whereas the hand function decreased after 8 weeks in the control group. The same was true for neurophysiological measures like the amplitude and the action potential. All the differences were significant in favor of the group treated with PEA. [21]

The Costen Syndrome or temporomandibular syndrome (TMD) is a condition that causes chronic pain in the jaw joint and/or muscles around the joint. 2 groups of patients were treated in a randomized study, both suffering from considerable pain and with trouble opening the mouth. Half of them were treated with a classical (NSAID) painkiller, 600mg of Ibuprofen three times a day. The other half was treated with 900mg of palmitoylethanolamide, a bodily substance without notable side effects or interactions. The results were impressive. The treatment with PEA not only significantly reduced the pain, but the jaw function and opening the mouth was better compared to the group treated with ibuprofen. [22]

An open study gave 8 patients with post-herpetic pain in the face 0,3% PEA cream. The patients applied the cream on the painful areas of the face 2 times a day for 2-4 weeks. 5 out of 8 patients experienced an average pain reduction of 87.8%. [23] All patients for whom the pain lasted shorter than one month also reported a clear pain reduction.

Furthermore, according to a number of case studies, PEA also shows to ease endometriosis pain. Specifically the pain that occurs during sexual intercourse. Four patients with endometriosis pain benefited from treatment with PEA. [24]

The treatment of endometriosis pain lasted for 90 days and used a combination of 400mg PEA and 40mg polydatin twice a day. They evaluated different types of pain: pelvis pain, pain during intercourse, pain during bowel movements, pain during urination and pain during menstruation. Pain relief was experienced within a month. On top of that the woman were able to reduce the amount of painkillers they took and an ultrasound scan showed a decrease of the endometriosis spots.

And lastly in another case study PEA showed to clearly decrease the pain of a 40-year-old patient with difficult to treat neuropathic pelvis pain. [25]


Summary and evaluation

Meanwhile over 200 patients have been treated with palmitoylethanolamide in the Netherlands, often in combination with other pain relief medicine like pregabaline. The patients have been very satisfied with the results. Since 2012 a very pure form of PEA has been available that is produced in the Netherlands under the name PeaPure.

Because the substance has been studied on many thousands of patients and been prescribed to more than a million patients, palmitoylethanolamide seems to offer and alternative treatment method to patients with MS that suffer from difficult to treat spasms and pains.

Palmitoylethanolamide has been studied with many pain syndromes and shows to be effective. Furthermore it can be easily combined with other medicine and the side effects are not problematic. That’s why we give a green light for this pain relieving body’s own substance. Because the substance wasn’t developed by the big pharmaceutical companies the studies have only been mentioned in Italian and Spanish journals or as abstracts in English journals. Experiences of Dutch patients with the substance against a variety of neuropathic pain syndromes have been documented on Youtube.


Appendix: nerve regeneration and palmitoylethanolamide

Animal models can help us understand what the value of certain substances could be. In a series of animal models information keeps surfacing that shows that palmitoylethanolamide not only has a pain relieving and anti-inflammatory effect but also promotes regeneration of the nervous system. This is incredibly important for patients with MS or paraplegia.

In a model for paraplegia, or damaged spinal cord, it was studied how palmitoylethanolamide could protect the nerve cells:

The aim of the present study was to carefully investigate molecular pathways and subtypes of glial cells involved in the protective effect of PEA on inflammatory reaction associated with an experimental model of SCI.

In this study they damaged the spine of a mouse, at the level of the chest. After the damage they gave the mouse palmitoylethanolamide. The substance turned out to protect the nerve cells in the damaged spine by inhibiting the inflammatory process (through the mast cells, amongst others). The substance also helped to improve the work of the natural recovery molecules:

Repeated PEA administration (10mg/kg i.p., 6 and 12h after SCI) significantly reduced the degree of the severity of spinal cord trauma through the reduction of mast cell infiltration and activation. Moreover, PEA treatment significantly reduced the activation of microglia and astrocytes expressing cannabinoid CB(2) receptor after SCI. Importantly, the protective effect of PEA involved changes in the expression of neurotrophic factors, and in spinal cord dopaminergic function.

The conclusion was:

Our results enhance our understanding about mechanisms related to the anti-inflammatory property of the PEA suggesting that this N-acylethanolamine may represent a crucial therapeutic intervention both diminishing the immune/inflammatory response and promoting the initiation of neurotrophic substance after spinal cord injury.  [26]

Other studies also show that palmitoylethanolamide and related substances can protect the nerve cells.[27] [28][29][30]



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