Nerveprotection in cancer treatment by palmitoylethanolamide

Palmitoylethanolamide (PEA) is a nerve-protective and anti-inflammatory body own compound, under brandnames een PEA-houdend product and PeaPure available as a foodsupplement.

A study published in 2011 shows that nerve damage due to chemotherapy for Kahler’s disease can be reversed by a natural compound, PEA. The results were published today in the Journal CNS Neurol Disord Drug Targets by University of Rome researchers.

Palmitoylethanolamide in chemotherapy

Kahler’s disease is cancer of certain white blood cells and leads to death, mostly within 3-4 years. It is the second most frequent occuring form of blood cancer. Treatment is possible with modern chemotherapy, such as bortezomib and thalodomide, but side effects such as nerve dammage and nerve pain are very frequent (about 80%). Due to this nerve damage, optimal treatment of patients is not possible as the chemotherapy needs to be stopped or reduced in dose. Therfore patients cannot finish the full course of chemotherapy and run a higher risk for recurrence of cancer. For years science has been searching for compounds to protect nerve function, in order to enable patients suffering from bloodcancer to continue treatment with chemotherapy.

The study results, from a clinical trial in 20 blood cancer patients, showed that a natural occuring compound, palmitoylethanolamide (PEA), can protect nerves and decrease pain during chemotherapy.

Professor Cruccu and his coworkers treated blood cancer patients by adding PEA to the chemotherapy and found that nerve functions did not further deteriorate, but started to improve, and pain was significantly reduced.

This is a very important result, as it is the first study showing that protection of nerve functions against side effects of chemotherapy is possible and safe. The chance of succesful treatment for patients with this form of cancer is increased by these results. Palmitoylethanolamide is available for patients and its safety and efficacy has been established in 39 clinical trials in over 2000 patients.

Palmitoylethanolamide has been tested and found to bring relief to many patients suffering from sciatic pain, diabetic pain, backpain and many other neuropathic pain states. This is due to the fact that this body-own molecule reduces pathological overactivation of certain cells which trigger the nerves to generate pain, the mast cells and the glia cells.

Palmitoylethanolamide is present in an Italian formulation produced in Italy and introduced in the Italian and Spanish patients, and as PeaPure, a Dutch formulation, produced in the Netherlands and shipped to every country.

For more details see link

Some details on palmitoylethanolamide and cancer

The authors started with giving their rationale to treat chemotherapy patients with PEA:

Palmitoylethanolamide (PEA), an endogenous fatty acid amide [6, 7], reportedly inhibits the release of pro-inflammatory mediators from activated mast cells [8, 9] and reduces the recruitment and activation of mast cells at sites of nerve injury [10], resulting in anti-allodynic and anti-hyperalgesic effects in a model of europathic pain. In addition, after peripheral nerve injury as well as following spinal neuroinflammation or spinal cord injury, PEA treatment inhibited microglia activation [11, 12] and the recruitment of mast cells into spinal cord [13]. PEA effects on chronic and neuropathic pain symptoms have been confirmed in numerous clinical conditions [14-17]. Importantly, in patients suffering from entrapment neuropathy, PEA-induced reduction of pain intensity was also associated with a functional recovery of neuronal activity [18].

And after the positive results, they thought about the essence and stated:

A dysregulation between anti-inflammatory and inflammatory cytokines caused by bortezomib and thalidomide may contribute to the neuronal alterations. Bortezomib and thalidomide also inhibit the activation of nuclear factor-kB, thereby blocking the transcription of the trophic factor nerve growth factor [31]. Intriguingly, PEA has been reported to normalize the levels of trophic factors in the sciatic nerve following peripheral nerve damage caused by experimental chronic compression [10]. On the other hand, lesion or dysfunction of nerve fibers is known to activate endoneuronal mast cells, causing endoneural edema. The resulting endoneural edema is probably responsible both for axonal degeneration and conduction block [32-34].
PEA is known to modulate the hyperactivity of endoneural mast cells, thus favouring the physiological balance between anti- inflammatory and inflammatory cytokines. In particular, the fatty acid amide could regulate trophic support for neurons while limiting environmental conditions that favour endoneural edema leading to conduction block [7, 30, 35]. Conceivably PEA, by modulating endoneural mast cells may limit the lack of trophic factors as well as the endoneural edema, thereby reducing the number of nerve axons unable to conduct. Although we do not have any indication that PEA favoured nerve regeneration, a direct protective action of PEA cannot be completely ruled out given its reported neuroprotective action on neurons [36, 37].

References on PEA

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[32] Lundborg, G.; Myers, R.; Powell, H. Nerve compression injury and increased endoneurial fluid pressure: a “miniature compartment syndrome”. J. Neurol. Neurosurg. Psychiatry, 1983, 46, 1119- 1124.
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[34] Mizisin, A.P.; Weerasuriya, A. Homeostatic regulation of the endoneurial microenvironment during development, aging and in response to trauma, disease and toxic insult. Acta Neuropathol., 2011, 121, 291-312.
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[37] Koch, M.; Kreutz, S.; Böttger, C.; Benz, A.; Maronde, E.; Ghadban, C.; Korf, H.W.; Dehghani, F. Palmitoylethanolamide protects dentate gyrus granule cells via peroxisome proliferator- activated receptor-alpha. Neurotox. Res., 2011, 19(2), 330-340.

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