Palmitoylethanolamide (PeaPure, Normast) is a natural compound, proven to be effective and safe in a great mumber of indications, related to chronic pain and inflammation. These disorders are all summerized in this figure.
Palmitoylethanolamide is a body’s own molecule, that is obtainable as the supplement PeaPure®. This natural anti-inflammatory agent has a painkilling effect and virtually no side effects. At this moment, over a 1000 patients have been treated with this supplement in the Netherlands. For many of them, who suffered from untreatable pains and conditions, the results were and are still very positive.
Palmitoylethanolamide: Natural Molecule: 300.000.000 years development time
The functionality of palmitoylethanolamide in our body is a very special one. The molecule had the opportunity to develop itself in a natural way for over 300 million years, inside the bodies of many different kinds of animals. That is why it can be so very helpful in treating severe pains in dogs, as well as neuropathic pains in people.
Palmitoylethanolamide works inside our cells on many different levels. It penetrates the nucleus of the cell and limits the activity of the so-called mast cells (certain inflammatory cells). It also influences the functioning of a specific important receptor that is located inside the nucleus. This receptor is called the PARR-receptor and by influencing it, palmitoylethanolamide fights inflammations and pain. This is why the agent can be helpful in cases of so many different diseases and conditions, that cause chronic pain and/or inflammations.
In the figure above you will find the ‘potential circle of indications’ for palmitoylethanolamide. This circle is based on pharmacological studies, preclinical studies on animals and on experience, gained at the Institute for Neuropathic Pain in the Netherlands and in the coalition for chronic pain. The circle of indications has been designed as a guideline for patients and professionals.
Circle of indications for palmitoylethanolamide
Because palmitoylethanolamide limits the activity of the so-called mast cells [1] and of the nerve- and glia cells that cause problems in cases of chronic pain, the following indications for this agent are understandable when you keep in mind their pathogenesis. The limitation of the distortion of the mast cells and other inflammatory cells, happens through the PARR-receptor. [2] [3] [4]
Chronic pain syndromes
- Chronic pain syndrome [5] [6] [7] [8] [9] [8] [11] [12] [13] [14] [15] [16] [17] [18]
- Bladder pain
- Diabetic neuropathic pain [19]
- Pain due to shingles (Herpes Zoster) [20] Deslo. P. Combination of pregabalin and palmitoylethanolamide (PEA) for neuropathic pain treatment.; Pathos, 2010, 17,4:9-14
- Neuropathic pain due to different kinds of neuropathy, CIAP, CIDP, etc. [12]
- Carpal Tunnel Syndrome (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; http://onlinelibrary.wiley.com/doi/10.1111/ene.2010.17.issue-s3/issuetoc; Eur J Neurol; 2010: 17(S3):295.) [22]
- Regional Pain Syndrome, Sudeck [23]
- Pain and painful spasms due to multiple sclerosis [24] [25] [26] [27] [28] [29] [30] [31] [32] [33] [34]
- Central neuropathic pain due to a stroke [35] [36] [37] [38] [39]
- Central neuropathic pain due to syringomyelia and paraplegics [24] [41]
- Migraine [42] [43] [44] [45]
- Fibromyalgia [46]
- Reumatism; Rheumatoid arthritis en pain due to Bechterew’s disease [47] [48] [49]
- Psoriatic arthritis [50]
- Costen’s Syndrome, Temporomandibular Joint Disorder (Bortolotti F,Russo M, Bartolucci ML, Alessandri Bonetti G, Gatto MR, Marini I.; Palmitoylethanolamide vs NSAID in the treatment of TMJD Pain; http://www.neuropathie.nu/documenten/wetenschappelijke-artikelen-engels/palmitoylethanolamide-bij-kaakpijn/details.html; Journal of Dental Research; 2010: 89(Special Issue B)
- Chronic pruritus (Itchy Bottom) [51]
- Pain and itching due to chemotherapy [52]
Urogenital Pain Syndromes (bladder, prostate, vagina)
When the urologist has excluded the possibility of cancer and when there are no bacteria causing the chronic infection, but there is a painful inflammation due to an unclear cause, than Normast® can be helpful. This agent regulates the overactivity of the inflammatory cells and it reduces the pain.
Chronic painful prostate complaints
- Chronic painful prostate complaints (prostatodynia) [53] [53] [55]
If the gynaecologist or urologist has excluded any infections, and when there is an inflammation on the inside of the bladder, that is accompanied by pain, trouble urinating and urinating small amounts, than treatment with Normast® can have a successful result.
Interstitial cystitis and bladder pain
Pain, burning sensations and inflammations of the vagina and vulva, gynaecological problems
- Lichen planus accompanied by itching and pain [62]
- Vulvovestibulitis [63] [64] [65]
- Vulvodynia, vestibulodynia [66] [67]
- Perineodynia (pain in the pelvis due to an unclear cause) [68]
- Endometriosis [69]
Gastrointestinal indications
- Intestinal inflammations and pain syndromes [9] [71]
- Ulcerative colitis [72] [73] [74]
- Morbus Crohn [75] [76]
- Irritable Bowel Syndrome [77] [78]
- Proctitis [79] [80] [79]
- Chronic abdominal pain due to an unclear cause [82] [78]
Skinconditions
- Chronic inflammations of the skin due to an unclear cause [16] [85] [86] [87] [88]
- Chronic itching due to an unclear cause [89] [51]
- Atopic and contact dermatitis [91] [92] [93] [94] [95] [96] [97]
- Psoriasis [98] [99] [100]
- Notalgia paresthetica (also through local creams, such as Algonerv)
Other conditions
- Asthma and COPD [101] [102] [103]
- Hay fever and allergic rhinitis [104]
- Angina pectoris and Kounis syndrome [105] [106] [107]
- Progressive arteriosclerosis [108]
- Ocular hypertension (high eyeball pressure) [109] [110]
- Depression [111]
- Parkinson’s disease [112]
- Alzheimer’s disease [113] [6]
- Paraplegics [24]
As said before, this circle has been designed as a guideline for colleagues. Part of the potential indications is only supported by data, based on animal studies, such as depression, paraplegics, Parkinson’s disease and Alzheimer’s disease.
References on Potential medical indications for palmitoylethanolamide (Normast)
-
1.
Weller CL, Collington SJ, Williams T, Lamb JRClin Sci (Lond). 2011 Jun 120(11)473-84 -
2.
Yamashita MPPAR Res. 2008 2008293538 -
3.
Cabrero A, Laguna JC, Vázquez MCurr Drug Targets Inflamm Allergy. 2002 Sep 1(3)243-8 -
4.
Tachibana M, Wada K, Katayama K, Kamisaki Y, Maeyama K, Blumberg RS, Nakajima AAllergy. 2008 Sep 63(9)1136-47 -
5.
D’Agostino G, La Rana G, Russo R, Sasso O, Iacono A, Mattace Raso G, Cuzzocrea S, Loverme JEur J Pharmacol. 2009 Jun 24 613(1-3)54-9 -
6.
Scuderi C, Esposito G, Blasio A, Valenza M, Arietti P, Carnuccio R, De Filippis D, Petrosino SJ Cell Mol Med. 2011 Jan 21 doi:10.1111/j.1582-4934.2011.01267.x -
7.
Cerrato S, Brazis P, della Valle MF, Miolo A, Puigdemont AVet Immunol Immunopathol. 2010 Jan 15 133(1)9-15 -
8.
Costa B, Comelli F, Bettoni I, Colleoni M, Giagnoni GPain. 2008 Oct 31 139(3)541-50 -
9.
De Filippis D, D’Amico A, Iuvone TJ Neuroendocrinol. 2008 May 2020-5 -
10.
Costa B, Comelli F, Bettoni I, Colleoni M, Giagnoni GPain. 2008 Oct 31 139(3)541-50 -
11.
Jhaveri MD, Richardson D, Robinson I, Garle MJ, Patel A, Sagar DR, Bennett AJ, Alexander SPNeuropharmacology. 2008 Jul 55(1)85-93 -
12.
Wallace VC, Segerdahl AR, Lambert DM, Vandevoorde S, Blackbeard J, Hasnie F, Rice ASBr J Pharmacol. 2007 Aug 151(7)1117-28 -
13.
LoVerme J, Russo R, La Rana G, Fu J, Farthing J, Meli R, Hohmann A, Calignano AJ Pharmacol Exp Ther. 2006 Dec 319(3)1051-61 -
14.
Farquhar-Smith WP, Rice ASAnesthesiology. 2001 Mar 94(3)507-13; discussion 6 -
15.
Jaggar SI, Hasnie FS, Sellaturay S, Rice ASPain. 1998 May 76(1-2)189-99 -
16.
De Filippis D, Luongo L, Cipriano M, Palazzo E, Cinelli MP, Maione S, Iuvone TMol Pain. 2011 73 -
17.
Matzke AJ, Weiger TM, Matzke MAFEBS Lett. 1990 Oct 1 271(1-2)161-4 -
18.
Ford GK, Kieran S, Dolan K, Harhen B, Finn DPPain. 2011 Aug 22 -
19.
Matias I, Wang JW, Moriello AS, Nieves A, Woodward DFProstaglandins Leukot Essent Fatty Acids. 2006 Dec 75(6)413-8 -
20.
Phan NQ, Siepmann D, Gralow I, Ständer SJ Dtsch Dermatol Ges. 2010 Feb 8(2)88-91 -
21.
Wallace VC, Segerdahl AR, Lambert DM, Vandevoorde S, Blackbeard J, Hasnie F, Rice ASBr J Pharmacol. 2007 Aug 151(7)1117-28 -
22.
Conigliaro R, Drago V, Foster PS, Schievano C, Di Marzo VMinerva Med. 2011 Apr 102(2)141-7 -
23.
Islam MS, Nilsson T, Rorsman P, Berggren POFEBS Lett. 1991 Aug 19 288(1-2)27-9 -
24.
Esposito E, Paterniti I, Mazzon E, Genovese T, Di Paola R, Cuzzocrea SBrain Behav Immun. 2011 Feb 25 -
25.
Jean-Gilles L, Feng S, Tench CR, Chapman V, Kendall DA, Constantinescu CSJ Neurol Sci. 2009 Dec 15 287(1-2)212-5 -
26.
Zajicek JP, Apostu VICNS Drugs. 2011 Mar 1 25(3)187-201 doi:10.2165/11539000-000000000-00000 -
27.
Loría F, Petrosino S, Mestre L, Spagnolo A, Correa F, Guaza C, Di Marzo V, Docagne FEur J Neurosci. 2008 Aug 28(4)633-41 -
28.
Cabranes A, Venderova K, de Lago E, Fezza F, Sánchez A, Valenti M, García-Merino A, Ramos JANeurobiol Dis. 2005 Nov 20(2)207-17 -
29.
Maccarrone M, Bernardi G, Agrò AF, Centonze DBr J Pharmacol. 2011 Aug 163(7)1379-90 doi:10.1111/j.1476-5381.2011.01277.x -
30.
Bisogno T, Di Marzo VCNS Neurol Disord Drug Targets. 2010 Nov 9(5)564-73 -
31.
Correa F, Hernangómez-Herrero M, Mestre L, Loría F, Docagne FBrain Behav Immun. 2011 May 25(4)736-49 -
32.
Rossi S, Bernardi G, Centonze DExp Neurol. 2010 Jul 224(1)92-102 -
33.
Loría F, Petrosino S, Hernangómez M, Mestre L, Spagnolo A, Di Marzo V, Docagne F, Guaza CNeurobiol Dis. 2010 Jan 37(1)166-76 -
34.
Correa FG, Mestre L, Docagne F, Borrell J, Guaza CVitam Horm. 2009 81207-30 -
35.
Naccarato M, Pizzuti D, Petrosino S, Simonetto M, Ferigo L, Pizzolato G, Di Marzo VLipids Health Dis. 2010 947 -
36.
Hansen HSExp Neurol. 2010 Jul 224(1)48-55 -
37.
Koch M, Kreutz S, Böttger C, Benz A, Maronde E, Korf HW, Dehghani FNeurotox Res. 2011 Feb 19(2)330-40 -
38.
Schomacher M, Müller HD, Sommer C, Schwab S, Schäbitz WRBrain Res. 2008 Nov 13 1240213-20 -
39.
Gray E, Ginty M, Kemp K, Scolding N, Wilkins AEur J Neurosci. 2011 Apr 33(8)1421-32 doi:10.1111/j.1460-9568.2011.07637.x -
40.
Esposito E, Paterniti I, Mazzon E, Genovese T, Di Paola R, Cuzzocrea SBrain Behav Immun. 2011 Feb 25 -
41.
Genovese T, Esposito E, Mazzon E, Di Paola R, Meli R, Piomelli D, Calignano A, Cuzzocrea SJ Pharmacol Exp Ther. 2008 Jul 326(1)12-23 -
42.
Sarchielli P, Pini LA, Coppola F, Rossi C, Baldi A, Calabresi PNeuropsychopharmacology. 2007 Jun 32(6)1384-90 -
43.
Levy DCurr Pain Headache Rep. 2009 Jun 13(3)237-40 -
44.
Levy D, Burstein R, Strassman AMHeadache. 2006 Jun 46S13-8 -
45.
Zhang XC, Strassman AM, Burstein R, Levy DJ Pharmacol Exp Ther. 2007 Aug 322(2)806-12 -
46.
Blanco I, Béritze N, Argüelles M, Cárcaba V, Fernández F, Oikonomopoulou K, de Serres FJ, Fernández-Bustillo EClin Rheumatol. 2010 Dec 29(12)1403-12 -
47.
Lee DM, Friend DS, Gurish MF, Benoist C, Mathis DScience. 2002 Sep 6 297(5587)1689-92 -
48.
Nigrovic PA, Lee DMNovartis Found Symp. 2005 271200-9; discussion 21 -
49.
Christy AL, Brown MAJ Immunol. 2007 Sep 1 179(5)2673-9 -
50.
Cañete JD, Celis R, Noordenbos T, Moll C, Gómez-Puerta JA, Palacin A, Tak PP, Sanmartí RArthritis Res Ther. 2009 11(1)R17 -
51.
Ständer S, Raap U, Weisshaar E, Schmelz M, Mettang T, Luger TAJ Dtsch Dermatol Ges. 2011 Jun 9(6)456-63 doi:10.1111/j.1610-0387.2011.07585.x -
52.
Latif S, Fraga G, Gadzia JJ Drugs Dermatol. 2010 Mar 9(3)268-70 -
53.
Papadoukakis S, Kyroudi-Voulgari A, Truss MC, Perea D, Mitropoulos DUrol Int. 2010 84(1)100-4 -
54.
Papadoukakis S, Kyroudi-Voulgari A, Truss MC, Perea D, Mitropoulos DUrol Int. 2010 84(1)100-4 -
55.
Mehik A, Leskinen MJ, Hellström PWorld J Urol. 2003 Jun 21(2)90-4 -
56.
Butrick CW, Howard FM, Sand PKJ Womens Health (Larchmt). 2010 Jun 19(6)1185-93 -
57.
Richter B, Roslind A, Hesse U, Nordling J, Johansen JS, Hansen ABHistopathology. 2010 Sep 57(3)371-83 doi:10.1111/j.1365-2559.2010.03640.x -
58.
Geurts N, Van Dyck J, Wyndaele JJScand J Urol Nephrol. 2011 Feb 45(1)20-3 -
59.
Richter B, Hesse U, Hansen AB, Horn T, Mortensen SOBJU Int. 2010 Mar 105(5)660-7 -
60.
Larsen MS, Mortensen S, Nordling J, Horn TBJU Int. 2008 Jul 102(2)204-7; discussion 20 -
61.
Rudick CN, Bryce PJ, Guichelaar LA, Berry RE, Klumpp DJPLoS One. 2008 3(5)e2096 -
62.
van de Nieuwenhof HP, Hebeda KM, Bulten J, Otte-Holler I, Massuger LF, van Kempen LCHistopathology. 2010 Sep 57(3)351-62 doi:10.1111/j.1365-2559.2010.03635.x -
63.
Bornstein J, Goldschmid N, Sabo EGynecol Obstet Invest. 2004 58(3)171-8 -
64.
Halperin R, Zehavi S, Vaknin Z, Ben-Ami I, Pansky MGynecol Obstet Invest. 2005 59(2)75-9 -
65.
Chadha S, Gianotten WL, Drogendijk AC, Weijmar Schultz WC, Blindeman LAInt J Gynecol Pathol. 1998 Jan 17(1)7-11 -
66.
Harlow BL, He W, Nguyen RHAnn Epidemiol. 2009 Nov 19(11)771-7 -
67.
Goetsch MF, Morgan TK, Korcheva VB, Li H, Peters DAm J Obstet Gynecol. 2010 Jun 202(6)614.e1-8 -
68.
Calabrò RS, Gervasi G, Marino S, Mondo PN, Bramanti PPain Med. 2010 May 11(5)781-4 -
69.
Indraccolo U, Barbieri FEur J Obstet Gynecol Reprod Biol. 2010 May 150(1)76-9 -
70.
De Filippis D, D’Amico A, Iuvone TJ Neuroendocrinol. 2008 May 2020-5 -
71.
Theoharides TC, Alysandratos KD, Angelidou A, Delivanis DA, Sismanopoulos N, Asadi S, Vasiadi M, Weng ZBiochim Biophys Acta. 2010 Dec 23 -
72.
Peterson CG, Sangfelt P, Wagner M, Hansson T, Lettesjö HScand J Clin Lab Invest. 2007 67(8)810-20 -
73.
Rognum TO, Brandtzaeg PInt Arch Allergy Appl Immunol. 1989 89(2-3)256-60 -
74.
O’Sullivan SE, Kendall DAImmunobiology. 2010 Aug 215(8)611-6 -
75.
Lakhan SE, Kirchgessner AJ Neuroinflammation. 2010 737 -
76.
Kraneveld AD, Rijnierse A, Nijkamp FP, Garssen JEur J Pharmacol. 2008 May 13 585(2-3)361-74 -
77.
Foley S, Garsed K, Singh G, Duroudier NP, Swan C, Zaitoun A, Bennett A, Marsden CGastroenterology. 2011 May 140(5)1434-43.e1 -
78.
Chang JY, Talley NJCurr Opin Gastroenterol. 2011 Jan 27(1)72-8 -
79.
Solorzano C, Zhu C, Battista N, Astarita G, Lodola A, Mor M, Russo R, Maccarrone MProc Natl Acad Sci U S A. 2009 Dec 8 106(49)20966-71 -
80.
Blirando K, Milliat F, Martelly I, Sabourin JC, Benderitter MAm J Pathol. 2011 Feb 178(2)640-51 -
81.
Solorzano C, Zhu C, Battista N, Astarita G, Lodola A, Mor M, Russo R, Maccarrone MProc Natl Acad Sci U S A. 2009 Dec 8 106(49)20966-71 -
82.
Taylor TJ, Youssef NN, Shankar R, Kleiner DE, Henderson WABMC Res Notes. 2010 3265 -
83.
Chang JY, Talley NJCurr Opin Gastroenterol. 2011 Jan 27(1)72-8 -
84.
De Filippis D, Luongo L, Cipriano M, Palazzo E, Cinelli MP, Maione S, Iuvone TMol Pain. 2011 73 -
85.
Petrosino S, Iuvone T, Di Marzo VBiochimie. 2010 Jun 92(6)724-7 -
86.
, De Filippis D, D’Amico A, Cipriano M, Petrosino S, Di Marzo V, Iuvone TPharmacol Res. 2010 Apr 61(4)321-8 -
87.
Hoareau L, Buyse M, Festy F, Ravanan P, Gonthier MP, Petrosino S, Tallet F, d’Hellencourt CLObesity (Silver Spring). 2009 Mar 17(3)431-8 -
88.
De Filippis D, D’Amico A, Cinelli MP, Esposito G, Di Marzo VJ Cell Mol Med. 2009 Jun 13(6)1086-95 -
89.
Machelska HArch Immunol Ther Exp (Warsz). 2011 Feb 59(1)11-24 -
90.
Ständer S, Raap U, Weisshaar E, Schmelz M, Mettang T, Luger TAJ Dtsch Dermatol Ges. 2011 Jun 9(6)456-63 doi:10.1111/j.1610-0387.2011.07585.x -
91.
Järvikallio A, Naukkarinen A, Harvima IT, Aalto ML, Horsmanheimo MBr J Dermatol. 1997 Jun 136(6)871-7 -
92.
Eberlein B, Eicke C, Reinhardt HW, Ring JJ Eur Acad Dermatol Venereol. 2008 Jan 22(1)73-82 -
93.
Petrosino S, Cristino L, Karsak M, Gaffal E, Ueda N, Bisogno T, De Filippis D, D’Amico AAllergy. 2010 Jun 1 65(6)698-711 -
94.
Kircik LJ Drugs Dermatol. 2010 Apr 9(4)334-8 -
95.
Hatano Y, Man MQ, Uchida Y, Crumrine D, Mauro TM, Elias PM, Holleran WMJ Allergy Clin Immunol. 2010 Jan 125(1)160-9.e1-5 -
96.
Dahten A, Koch C, Ernst D, Schnöller C, Hartmann SJ Invest Dermatol. 2008 Sep 128(9)2211-8 -
97.
Cerrato S, Brazis P, Valle MF, Miolo A, Petrosino S, Puigdemont AVet J. 2011 May 19 -
98.
Harvima IT, Nilsson G, Naukkarinen AG Ital Dermatol Venereol. 2010 Apr 145(2)195-204 -
99.
Kneilling M, Röcken MExp Dermatol. 2009 May 18(5)488-96 -
100.
Harvima IT, Nilsson G, Suttle MM, Naukkarinen AArch Dermatol Res. 2008 Oct 300(9)461-78 -
101.
Broide DH, Finkelman F, Bochner BS, Rothenberg MEJ Allergy Clin Immunol. 2011 Mar 127(3)689-95 -
102.
Di Capite JL, Bates GJ, Parekh ABCurr Opin Allergy Clin Immunol. 2011 Feb 11(1)33-8 -
103.
Zhao J, Endoh I, Hsu K, Tedla N, Endoh YAntioxid Redox Signal. 2011 May 1 14(9)1589-600 -
104.
Metz M, Gilles S, Geldmacher A, Behrendt H, Traidl-Hoffmann CJ Invest Dermatol. 2011 Apr 131(4)987-90 -
105.
Ozben B, Erdogan OInflamm Allergy Drug Targets. 2008 Sep 7(3)136-44 -
106.
Kounis NGInt J Cardiol. 2006 Jun 7 110(1)7-14 -
107.
-
108.
Wilensky RL, Hamamdzic DCurr Opin Cardiol. 2007 Nov 22(6)545-51 -
109.
Pescosolido N, Librando A, Puzzono M, Nebbioso MJ Ocul Pharmacol Ther. 2011 Aug 10 -
110.
Chen J, Matias I, Dinh T, Lu T, Venezia S, Woodward DF, Di Marzo VBiochem Biophys Res Commun. 2005 May 20 330(4)1062-7 -
111.
Yu HL, Deng XQ, Li YJ, Li YC, Quan ZSPharmacol Rep. 63(3)834-9 -
112.
Murillo-Rodríguez E, Palomero-Rivero M, Millán-Aldaco D, Arias-Carrión O, Drucker-Colín RPLoS One. 2011 6(7)e20766 -
113.
Romani R, Galeazzi R, Rosi G, Fiorini R, Pirisinu I, Zolese GBiochimie. 2011 Sep 93(9)1584-91 -
114.
Scuderi C, Esposito G, Blasio A, Valenza M, Arietti P, Carnuccio R, De Filippis D, Petrosino SJ Cell Mol Med. 2011 Jan 21 doi:10.1111/j.1582-4934.2011.01267.x -
115.
Esposito E, Paterniti I, Mazzon E, Genovese T, Di Paola R, Cuzzocrea SBrain Behav Immun. 2011 Feb 25