Endogenous natural pain reliever PEA for chronic pain, a breakthrough

Endogenous natural pain reliever PEA for chronic pain, a breakthrough

A pain reliever without side effects! Is it possible? Yes, if you take a substance produced by the body itself. PEA is such an endogenous substance, which makes it an exceptional pain reliever. For old and young.

PEA stands for palmitoylethanolamide. A proven effective, new pain reliever with anti-inflammatory effect, natural and endogenous, easy-to-use, also by the elderly, in combination with medication, and without problematic side effects.

Recent research shows that treatment with the endogenous analgesic substance PEA is better than treatment that makes use of painkillers (which are not good for the stomach) like ibuprofen (NSAIDs). And its efficacy has also been proven in recent studies in the occurrence of severe hernia pain, chronic diabetic pains, the carpal tunnel syndrome and chronic arthritis of the temporomandibular joint.

 

PEA (palmitoylethanolamide): a natural pain reliever

Treating chronic pain without having to suffer the annoying side effects caused by painkillers like brufen, pregabaline and amitriptyline. Without stomach haemorrhage, without dizziness, without that zombie-feeling many patients complain about. That is one of the benefits of a treatment with PEA, an exceptional analgesic substance produced by the body called palmitoylethanolamide, abbreviated PEA.

This substance activates the own natural immune system against pain, which is exceptional. The substance is known in medicine since it was discovered back in 1957, and has been tested in many dozens of studies with many thousands of patients. The substance always turned out to be a very effective and safe one.

A brief analysis of this exceptional substance.

It was high time for a new pain reliever to be introduced on the market, particularly since the rheumatologist showed in his dissertation that each year 5,100 people suffer from severe gastric bleeding caused by common painkillers, and that more than 500 of them die. With PEA we have finally a pain reliever of a new generation at hand, with extremely mild side effects. Also the elderly can take this medium without any problem, without fear of side effects or interactions.

 

PEA (palmitoylethanolamide) compared with ibuprofen

Osteoarthritis of the jaw joints, creaking jaws and a lot of pain. This is called Costen’s syndrome or temporomandibular joint dysfunction (TMD).

In an Italian research carried out by dentists at the University of Bologna (Department of Orthodontics, Dentistry, School of Dentistry, University of Bologna) two groups of patients with a lot of pain and who could hardly open their mouth because of Costen’s syndrome, were treated in a randomized study,

One half was treated with a classic painkiller, an NSAID, namely 600 mg ibuprofen three times per day. The other half was given a treatment with palmitoylethanolamide.

The results were impressive. The treatment with PEA resulted after only two weeks in not only significantly less pain, but it also turned out that the function of the jaw when opening of the mouth was better than in the ibuprofen treatment. [1]

Analgesic substances such as brufen and ibuprofen (NSAIDs) are often administered when treating TMD. But actually no pain reliever such as ibuprofen has proven effective for this pain syndrome! [2] PEA therefore is indeed a breakthrough.

 

PEA for pain caused by the carpal tunnel syndrome, hernia pain and diabetes pain

PEA has now been tested on a variety of chronic disorders and pain syndromes, and every time it proves to be a safe and meaningful pain reliever and treatment. [3][4][5][6][7][8]The largest study of PEA has been done with patients suffering from severe hernia pain. In a double-blind randomized study, more than 600 patients with a herniated disc were treated with either PEA or a placebo. The PEA dosage was 1200 mg per day over a period of 3 weeks. The study was carried out in 9 hospitals and university centres in Italy. After 3 weeks, the patients treated with PEA had clearly and significantly less pain than patients on placebo. [9]

 

PEA: recommended by Nobel Prize Winner

Already 20 years ago, the body’s own substance palmitoylethanolamide was indicated as an exceptional substance against severe neuropathic pain by the Italian professor Rita Levi-Montalcini, a Nobel Prize Winner.

Many hundreds of scientific studies have been carried out on this substance by all kinds of biologists, physiologists, and doctors. Doctors can find a lot of information about PEA.

The recommendations of Professor Levi-Montalcini were followed, and palmitoylethanolamide was further examined in case of severe pains, pains that were not treatable with other substances.

 

Thousands of patients on PEA (palmitoylethanolamide)

Many hundreds of thousands of patients with severe pain have now been treated with this substance, very often with very good, even impressive results. PEA has proven to  be effective in relieving pain after a stroke, severe back pain, hernia pain, shingles pain, pain caused by pinched nerves, e.g. in case of  the carpal tunnel syndrome, and diabetes pain, to mention but a few severe pains. The substance can also be taken in combination with other pain relievers, if desired, because so far no interactions with other products have been found.

PEA has been tested for efficacy and safety in many different clinical studies.[10] [11] [4] [1][7][15][5] [17][18][19][20][21][22]

 

PEA (palmitoylethanolamide): also safely for the elderly

Many hundreds of old and very old patients have been treated, and no problems are reported in the field of drug interaction or side effects. In the U.S., the oldest patient being treated is 90 years old. She suffered from severe pain caused by a polyneuropathy. She left a few months after having started using PEA for Canada to visit her grandchildren. By then, the pain intensity had decreased by more than 50%.

The endogenous substance PEA is broken down in our body by an enzyme that is present in each cell, the so-called FAAH (fatty acid amide hydrolase). This means that the degradation does not affect kidney or liver and that kidney and liver patients can also use this analgesic substance.

 

PEA (palmitoylethanolamide): what is it and how to use?

PEA has no problematic side effects, because it is a substance produced by the body, and it can be taken with other medicines without any problem. There are no known drug interactions.

Because PEA is a substance produced by the body, and has no side effects and it is also working so well, many patients say they find it much nicer to take than for example amitriptyline, Lyrica, and that kind of pharmaceuticals, which make you often drowsy.

Because in case of chronic pain, PEA must replenish the natural palmitoylethanolamide-stock in the body, it usually starts to have effect after 1 to 3 weeks. To give the substance sufficient time to be effective, a trial period up to 6 weeks is recommended.

Start dosage: 1200-2400 mg PEA per day for 2 to 3 weeks.

PEA is, as has been said, a substance produced by the body, and until now no significant side effects can be found in literature. There are also no negative interactions to be expected. The substance has been examined with a large number of elderly patients, and so far no problems have been reported in this group either.

 

PEA (palmitoylethanolamide): a piece of science

PEA is a shorter and saturated analogue of the anandamid lipid and belongs to the family of the N-acylethanolamins. These molecules are found in many different tissues and in most mammals. [23] PEA accumulates in tissues as a biologically effective response to inflammation and chronic pain syndromes. Clinical data were collected in hernia pain, pain caused by Costen’s syndrome (temporomandibulary dysfunction, painful and creaking jaw joints), the carpal tunnel syndrome, and diabetic painful neuropathy.

The synthetic cannabinoidagonist nabilone and the NSAID indometacin were compared with PEA for an inflammatory model in which a rat got an acute inflammation with swelling and pain behavior caused by an injection of carrageenan in the rear leg. Nabilone 2.5 mg kg, palmitoylethanolamide 10 mg/kg, and indomethacin 5 mg/kg, administered an hour before the challenge, could clearly reduce the pain behavior. Administering a selective CB(2) cannabinoid receptor antagonist prior to nabilone and PEA counteracted that effect. [24]

In the Sixties of the previous century, the substance was already examined in models for pain relief and inflammatory diseases, such as for example the carrageenan induced edema of the rat’s leg. [25][26] At that time, there were a lot of publications by Czech researchers on the substance as a booster for the non-specific immune system. [27][28] This resulted in clinical studies with children and adults to get an impression whether PEA could prevent the flu, what it actually seemed to be able to do. Back then, the substance was known as Impulsin. [18][19][20]

PEA is an inflammation regulating and pain relieving molecule, which is produced in many different tissues, in neurons and even in the retina, in glia and also in white blood cells such as macrophages and basophils. [32][33][34] In a biological model for antigen-induced degranulation PEA seemed to have a measurable and significantly stabilizing effect. [35] Latest data are even more promising: PEA acts as a painkiller through the effect on an important core receptor, the so-called PPAR-alpha receptor. [36] This is currently a ‘hot’ topic for many pharmaceutical industries.

An impressive level of pre-clinical research has been done on this molecule. More than 350 scientific studies and many individual cases (anno August 2013)! [37] [38] It also seems to be a good option against fibromyalgia pain. [39]

Conclusion

In the meantime, more than a million patients have been treated with PEA, and in many different studies (with many thousands of patients) it proved to possess anti-inflammatory and pain relieving effects. Also the safety of the substance has been clearly indicated, hence a green light for PEA in the event of chronic pain. Problematic side effects or negative effects on other medicines with this substance produced by the body are not known of.

References

[1] Bortolotti F,Russo M, Bartolucci ML, Alessandri Bonetti G, Gatto MR, Marini I. | Palmitoylethanolamide vs NSAID in the treatment of TMJD Pain | Journal of Dental Research | 2010: 89(Special Issue B)

[2] Mujakperuo HR, Watson M, Morrison R, Macfarlane TV. | Pharmacological interventions for pain in patients with temporomandibular disorders. | Cochrane Database Syst Rev. | 2010 Oct 6;(10):CD004715. doi: 10.1002/14651858.CD004715.pub2.

[3] G. Guida, A. de Fabiani, F. Lanaia, A. Alexandre, G.M. Vassallo, L. Cantieri, M. de Martino, M. Rogai, S. Petrosino | La palmitoiletanolamida (PEA) en el dolor neuropatico cronico por lumbociatalgia de tipo compresivo: estudio clinico multicentrico. | Dolor:2010, 25:35-42

[4] Assini A, Laricchia D, Pizzo R, Pandolfini L, Belletti M, Colucci M, Ratto S. | P1577: The carpal tunnel syndrome in diabetes: clinical and electrophysiological improvement after treatment with palmitoylethanolamide | Eur J Neurol | 2010: 17(S3):295.

[5] Calabrò RS, Gervasi G, Marino S, Mondo PN, Bramanti P. | Misdiagnosed chronic pelvic pain: pudendal neuralgia responding to a novel use of palmitoylethanolamide. | Pain Med. | 2010 May;11(5):781-4. doi: 10.1111/j.1526-4637.2010.00823.x. Epub 2010 Mar 22.

[6] Petrosino S, Iuvone T, Di Marzo V. | N-palmitoyl-ethanolamine: Biochemistry and new therapeutic opportunities. | Biochimie. | 2010 Jun;92(6):724-7. doi: 10.1016/j.biochi.2010.01.006. Epub 2010 Jan 21.

[7] Phan NQ, Siepmann D, Gralow I, Ständer S. | Adjuvant topical therapy with a cannabinoid receptor agonist in facial postherpetic neuralgia. | J Dtsch Dermatol Ges. | 2010 Feb;8(2):88-91. doi: 10.1111/j.1610-0387.2009.07213.x. Epub 2009 Sep 10.

[8] Kircik L. | A nonsteroidal lamellar matrix cream containing palmitoylethanolamide for the treatment of atopic dermatitis. | J Drugs Dermatol. | 2010 Apr;9(4):334-8.

[9] G. Guida, A. de Fabiani, F. Lanaia, A. Alexandre, G.M. Vassallo, L. Cantieri, M. de Martino, M. Rogai, S. Petrosino | La palmitoiletanolamida (PEA) en el dolor neuropatico cronico por lumbociatalgia de tipo compresivo: estudio clinico multicentrico. | Dolor | 2010, 25:35-42

[10] G. Guida, A. de Fabiani, F. Lanaia, A. Alexandre, G.M. Vassallo, L. Cantieri, M. de Martino, M. Rogai, S. Petrosino | La palmitoiletanolamida (Normast) en el dolor neuropatico cronico por lumbociatalgia de tipo compresivo: estudio clinico multicentrico. | Dolor | 2010, 25:35-42

[11] Biasiotta A, La Cesa S, Leone C, Di Stefano G, Truini A, Cruccu G. | Efficacy of palmitoylethanolamide in patients with painful neuropathy. A clincial and neurophysiological open study. Preliminary results. | , Volume 4, Issue 1, May 2010, Page 77.

[12] Assini A, Laricchia D, Pizzo R, Pandolfini L, Belletti M, Colucci M, Ratto S. | P1577: The carpal tunnel syndrome in diabetes: clinical and electrophysiological improvement after treatment with palmitoylethanolamide | Eur J Neurol | 2010: 17(S3):295.

[13] Bortolotti F,Russo M, Bartolucci ML, Alessandri Bonetti G, Gatto MR, Marini I. | Palmitoylethanolamide vs NSAID in the treatment of TMJD Pain | Journal of Dental Research | 2010: 89(Special Issue B)

[14] Phan NQ, Siepmann D, Gralow I, Ständer S. | Adjuvant topical therapy with a cannabinoid receptor agonist in facial postherpetic neuralgia. | J Dtsch Dermatol Ges. | 2010 Feb;8(2):88-91. doi: 10.1111/j.1610-0387.2009.07213.x. Epub 2009 Sep 10.

[15] Indraccolo U, Barbieri F. | Effect of palmitoylethanolamide-polydatin combination on chronic pelvic pain associated with endometriosis: preliminary observations. | Eur J Obstet Gynecol Reprod Biol. | 2010 May;150(1):76-9. doi: 10.1016/j.ejogrb.2010.01.008. Epub 2010 Feb 21.

[16] Calabrò RS, Gervasi G, Marino S, Mondo PN, Bramanti P. | Misdiagnosed chronic pelvic pain: pudendal neuralgia responding to a novel use of palmitoylethanolamide. | Pain Med. | 2010 May;11(5):781-4. doi: 10.1111/j.1526-4637.2010.00823.x. Epub 2010 Mar 22.

[17]

[18] Masek K, Perlík F, Klíma J, Kahlich R. | Prophylactic efficacy of N-2-hydroxyethyl palmitamide (impulsin) in acute respiratory tract infections. | Eur J Clin Pharmacol. | 1974 Oct 4;7(6):415-9.

[19] Kahlich R, Klíma J, Cihla F, Franková V, Masek K, Rosický M, Matousek F, Bruthans J. | Studies on prophylactic efficacy of N-2-hydroxyethyl palmitamide (Impulsin) in acute respiratory infections. Serologically controlled field trials. | J Hyg Epidemiol Microbiol Immunol. | 1979;23(1):11-24.

[20] Wiedermannová D, Wiedermann D, Lokaj J. | [Prophylactic administration of impulsin to clinically healthy children.–effect on the serum proteins and metabolic activity of granulocytes (author’s transl)]. | Cas Lek Cesk. | 1978 Aug 18;117(33):1030-4.

[21] Eberlein B, Eicke C, Reinhardt HW, Ring J. | Adjuvant treatment of atopic eczema: assessment of an emollient containing N-palmitoylethanolamine (ATOPA study). | J Eur Acad Dermatol Venereol. | 2008 Jan;22(1):73-82. doi: 10.1111/j.1468-3083.2007.02351.x.

[22] Pulvirenti N, Nasca MR, Micali G. | Topical adelmidrol 2% emulsion, a novel aliamide, in the treatment of mild atopic dermatitis in pediatric subjects: a pilot study. | Acta Dermatovenerol Croat. | 2007;15(2):80-3.

[23] Lambert DM, Vandevoorde S, Jonsson KO, Fowler CJ. | The palmitoylethanolamide family: a new class of anti-inflammatory agents? | Curr Med Chem. | 2002 Mar;9(6):663-74.

[24] Conti S, Costa B, Colleoni M, Parolaro D, Giagnoni G. | Antiinflammatory action of endocannabinoid palmitoylethanolamide and the synthetic cannabinoid nabilone in a model of acute inflammation in the rat. | Br J Pharmacol. | 2002 Jan;135(1):181-7.

[25] Benvenuti F, Lattanzi F, De Gori A, Tarli P. | [Activity of some derivatives of palmitoylethanolamide on carragenine-induced edema in the rat paw]. | Boll Soc Ital Biol Sper. | 1968 May 15;44(9):809-13.

[26] Calignano A, La Rana G, Giuffrida A, Piomelli D. | Control of pain initiation by endogenous cannabinoids. | Nature. | 1998 Jul 16;394(6690):277-81.

[27] Rasková H, Masek K, Linèt O. | Non-specific resistance induced by palmitoylethanolamide. | Toxicon. | 1972 Aug;10(5):485-90.

[28] Hurych J, Holusa R, Effenbergerová E, Mirejovská E. | Attempt to influence silicotic fibrosis by means of N-(2-hydroxyethyl) palmitamide (Impulsin). | Czech Med. | 1980;3(3):218-25.

[29] Masek K, Perlík F, Klíma J, Kahlich R. | Prophylactic efficacy of N-2-hydroxyethyl palmitamide (impulsin) in acute respiratory tract infections. | Eur J Clin Pharmacol. | 1974 Oct 4;7(6):415-9.

[30] Kahlich R, Klíma J, Cihla F, Franková V, Masek K, Rosický M, Matousek F, Bruthans J. | Studies on prophylactic efficacy of N-2-hydroxyethyl palmitamide (Impulsin) in acute respiratory infections. Serologically controlled field trials. | J Hyg Epidemiol Microbiol Immunol. | 1979;23(1):11-24.

[31] Wiedermannová D, Wiedermann D, Lokaj J. | [Prophylactic administration of impulsin to clinically healthy children.–effect on the serum proteins and metabolic activity of granulocytes (author’s transl)]. | Cas Lek Cesk. | 1978 Aug 18;117(33):1030-4.

[32] Bisogno T, Maurelli S, Melck D, De Petrocellis L, Di Marzo V. | Biosynthesis, uptake, and degradation of anandamide and palmitoylethanolamide in leukocytes. | J Biol Chem. | 1997 Feb 7;272(6):3315-23.

[33] Matsuda S, Kanemitsu N, Nakamura A, Mimura Y, Ueda N, Kurahashi Y, Yamamoto S. | Metabolism of anandamide, an endogenous cannabinoid receptor ligand, in porcine ocular tissues. | Exp Eye Res. | 1997 May;64(5):707-11.

[34] Facci L, Dal Toso R, Romanello S, Buriani A, Skaper SD, Leon A. | Mast cells express a peripheral cannabinoid receptor with differential sensitivity to anandamide and palmitoylethanolamide. | Proc Natl Acad Sci U S A. | 1995 Apr 11;92(8):3376-80.

[35] Granberg M, Fowler CJ, Jacobsson SO. | Effects of the cannabimimetic fatty acid derivatives 2-arachidonoylglycerol, anandamide, palmitoylethanolamide and methanandamide upon IgE-dependent antigen-induced beta-hexosaminidase, serotonin and TNF alpha release from rat RBL-2H3 basophilic leukaemic cells. | Naunyn Schmiedebergs Arch Pharmacol. | 2001 Jul;364(1):66-73.

[36] Matzke AJ, Weiger TM, Matzke MA. | Detection of a large cation-selective channel in nuclear envelopes of avian erythrocytes. | FEBS Lett. | 1990 Oct 1;271(1-2):161-4.

[37] Bettoni I, Comelli F, Colombo A, Bonfanti P, Costa B. | Non-neuronal cell modulation relieves neuropathic pain: efficacy of the endogenous lipid palmitoylethanolamide. | CNS Neurol Disord Drug Targets. | 2013 Feb 1;12(1):34-44.

[38] Di Cesare Mannelli L, D’Agostino G, Pacini A, Russo R, Zanardelli M, Ghelardini C, Calignano A. | Palmitoylethanolamide is a disease-modifying agent in peripheral neuropathy: pain relief and neuroprotection share a PPAR-alpha-mediated mechanism. | Mediators Inflamm. | 2013;2013:328797. doi: 10.1155/2013/328797. Epub 2013 Feb 25.

[39] Ghafouri N, Ghafouri B, Larsson B, Stensson N, Fowler CJ, Gerdle B. | Palmitoylethanolamide and stearoylethanolamide levels in the interstitium of the trapezius muscle of women with chronic widespread pain and chronic neck-shoulder pain correlate with pain intensity and sensitivity. | Pain. | 2013 Sep;154(9):1649-58. doi: 10.1016/j.pain.2013.05.002. Epub 2013 May 14.