PEA an overview of the indications

We have most publications on file, available per request.


Chronic pain syndromes


Carpal tunnel syndrome

[1],[2] Central neuropathic pain by syringomyelia and spinal cord lesions[3],[4] Central neuropathic pain due to stroke[5],[6],[7],[8],[9] Chemotherapy-induced neuropathic pain[10]
Chronic idiopathic axonal neuropathy pain[11]
Chronic pruritus of unknown origin; unexplained itching
Common chronic pain syndromes[12],[13],[14],[15],[16],[17],[18],[19],[20],[21],[22],[23],[24],[25],[26],[27],[28],[29] Complex regional pain syndrome, Sudeck[30]
Costen’s syndrome, arthritis of the jaw, temporomandibular pain syndrome[31],[32] Diabetic neuropathic pain[33],[34],[35],[36],[37],[38] Fibromyalgia[39],[40] Hernia pain and back pain[41],[42],[43],[44],[45] Herpes zoster pain (shingles pain)[46],[47] Migraine[48],[49],[50],[51] Neuropathic pain in various types of neuropathy, CIAP, CIDP, etc.[52],[53],[54],[55],[56] Occipital neuralgia[57],[58] Pain and itching after chemotherapy[59]
Pain and painful spasms in multiple sclerosis[60],[61],[62],[63],[64],[65],[66],[67],[68],[69],[70],[71],[72] Psoriatic arthritis[73]
Rheumatism: rheumatoid arthritis and spondylitis pain[74],[75],[76] Visceral pain syndromes[77],[78],[79],[80]


Chronic painful prostate problems


Chronic prostate pain symptoms (prostatodynia)[81],[82]


Interstitial cystitis and bladder pain


Chronic bladder pain of unknown origin[83],[84],[85],[86],[87] Interstitial cystitis[88],[89]


Pain, burning and inflammations of the vagina, vulva & other gynecological indications


Endometriosis[90],[91],[92],[93] Lichen planus with itching and pain[94]
Menstruation pains[95]
Perineodynia (unexplained pelvic pain)[96]
Vulvodynia, vestibulodynia[97],[98],[99],[100] Vulvovestibulitis[101],[102],[103],[104]


Uroprotective benefits


Kidney protection[105]


Gastrointestinal indications


Chronic unexplained abdominal pain[106],[107] Crohn’s Disease[108],[109],[110] Intestinal (gut) inflammation and pain syndromes[111],[112],[113],[114],[115],[116],[117] Irritable bowel syndrome[118],[119] Proctitis[120],[121] Ulcerative colitis[122],[123],[124],[125],[126]


Skin disorders


Atopic and contact dermatitis[127],[128],[129],[130],[131],[132],[133],[134] Chronic unexplained itching[135],[136] Psoriasis[137],[138],[139] Unexplained chronic skin inflammation[140],[141],[142],[143],[144]


Neuroprotection, neuroinflammation, neuroregeneration


Neuroprotection and neuroregeneration[145],[146],[147],[148],[149],[150],[151] Neuroinflammation[152],[153]


Neurological and neuropsychiatric disorders


Alzheimer’s disease[154],[155],[156],[157],[158],[159],[160],[161] Amyotrophic lateral sclerosis (ALS)[162],[163] Blood pressure regulation[164]
Depression and anxiety[165],[166],[167],[168] Epilepsy[169],[170],[171] Ocular hypertension and glaucoma[172],[173],[174],[175] Parkinson’s disease[176]
Spinal cord injuries[177]
Stroke and spasticity[178],[179],[180] Uveitis[181]


Immunological benefits, infections, pulmonary disease


Asthma and COPD[182],[183],[184],[185] Flu and colds, infections[186],[187] Hay fever and allergic rhinitis[188] Strengthening immunological resistance[189]


Cardiovascular benefits


Angina pectoris and Kounis syndrome[190],[191],[192],[193],[194] Progression of atherosclerosis and hypertension[195],[196]


Generalized and other disorders and benefits


Addictions[197]
Arthritis[198]
Cancer (adjuvant) and cancer pain[199],[200],[201],[202],[203],[204],[205],[206],[207] Chronic inflammation in general[208],[209],[210],[211],[212],[213],[214],[215]


References


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[2] Conigliaro R, Drago V, Foster PS, Schievano C, Di Marzo V. Use of palmitoylethanolamide in the entrapment neuropathy of the median in the wrist. Minerva Med. 2011 Apr;102(2):141-7.
[3] Esposito E, Paterniti I, Mazzon E, Genovese T, Di Paola R, Galuppo M, Cuzzocrea S. Effects of palmitoylethanolamide on release of mast cell peptidases and neurotrophic factors after spinal cord injury. Brain Behav Immun. 2011 Aug;25(6):1099-112. doi: 10.1016/j.bbi.2011.02.006. Epub 2011 Feb 25.
[4] Genovese T, Esposito E, Mazzon E, Di Paola R, Meli R, Bramanti P, Piomelli D, Calignano A, Cuzzocrea S. Effects of palmitoylethanolamide on signaling pathways implicated in the development of spinal cord injury. J Pharmacol Exp Ther. 2008 Jul;326(1):12-23. Epub 2008 Mar 26.
[5] Naccarato M, Pizzuti D, Petrosino S, Simonetto M, Ferigo L, Grandi FC, Pizzolato G, Di Marzo V. Possible Anandamide and Palmitoylethanolamide involvement in human stroke. Lipids Health Dis. 2010 May 14;9:47.
[6] Hansen HS. Palmitoylethanolamide and other anandamide congeners. Proposed role in the diseased brain. Exp Neurol. 2010 Jul;224(1):48-55. Epub 2010 Mar 29.
[7] Koch M, Kreutz S, Böttger C, Benz A, Maronde E, Ghadban C, Korf HW, Dehghani F. Palmitoylethanolamide protects dentate gyrus granule cells via peroxisome proliferator-activated receptor-alpha. Neurotox Res. 2011 Feb;19(2):330-40. Epub 2010 Mar 11.
[8] Schomacher M, Müller HD, Sommer C, Schwab S, Schäbitz WR. Endocannabinoids mediate neuroprotection after transient focal cerebral ischemia. Brain Res. 2008 Nov 13;1240:213-20. Epub 2008 Sep 18.
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[10] Truini A1, Biasiotta A, Di Stefano G, La Cesa S, Leone C, Cartoni C, Federico V, Petrucci MT, Cruccu G. Palmitoylethanolamide restores myelinated-fibre function in patients with chemotherapy-induced painful neuropathy. CNS Neurol Disord Drug Targets. 2011 Dec;10(8):916-20.
[11] Hesselink JM. Chronic idiopathic axonal neuropathy and pain, treated with the endogenous lipid mediator palmitoylethanolamide: a case collection. Int Med Case Rep J. 2013 Sep 13;6:49-53. doi: 10.2147/IMCRJ.S51572.
[12] DiPaolo A et al. Palmitoylethanolamide as a treatment for vaious chronic painstates. Paper presented at the 34 AISD congress in Riccione, 2011.
[13] D’Agostino G, La Rana G, Russo R, Sasso O, Iacono A, Esposito E, Mattace Raso G, Cuzzocrea S, Loverme J, Piomelli D, Meli R, Calignano A. Central administration of palmitoylethanolamide reduces hyperalgesia in mice via inhibition of NF-kappaB nuclear signalling in dorsal root ganglia. Eur J Pharmacol. 2009 Jun 24;613(1-3):54-9. Epub 2009 Apr 20.
[14] Scuderi C, Esposito G, Blasio A, Valenza M, Arietti P, Steardo L Jr, Carnuccio R, De Filippis D, Petrosino S, Iuvone T, Di Marzo V, Steardo L. Palmitoylethanolamide counteracts reactive astrogliosis induced by beta-amyloid peptide. J Cell Mol Med. 2011 Dec;15(12):2664-74. doi: 10.1111/j.1582-4934.2011.01267.x.
[15] Cerrato S, Brazis P, della Valle MF, Miolo A, Puigdemont A. Effects of palmitoylethanolamide on immunologically induced histamine, PGD2 and TNFalpha release from canine skin mast cells. Vet Immunol Immunopathol. 2010 Jan 15;133(1):9-15. Epub 2009 Jun 27.
[16] Costa B, Comelli F, Bettoni I, Colleoni M, Giagnoni G. The endogenous fatty acid amide, palmitoylethanolamide, has anti-allodynic and anti-hyperalgesic effects in a murine model of neuropathic pain: involvement of CB(1), TRPV1 and PPARgamma receptors and neurotrophic factors. Pain. 2008 Oct 31;139(3):541-50. Epub 2008 Jul 3.
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[18] Costa B, Comelli F, Bettoni I, Colleoni M, Giagnoni G. The endogenous fatty acid amide, palmitoylethanolamide, has anti-allodynic and anti-hyperalgesic effects in a murine model of neuropathic pain: involvement of CB(1), TRPV1 and PPARgamma receptors and neurotrophic factors. Pain. 2008 Oct 31;139(3):541-50. Epub 2008 Jul 3.
[19] Jhaveri MD, Richardson D, Robinson I, Garle MJ, Patel A, Sun Y, Sagar DR, Bennett AJ, Alexander SP, Kendall DA, Barrett DA, Chapman V. Inhibition of fatty acid amide hydrolase and cyclooxygenase-2 increases levels of endocannabinoid related molecules and produces analgesia via peroxisome proliferator-activated receptor-alpha in a model of inflammatory pain. Neuropharmacology. 2008 Jul;55(1):85-93. Epub 2008 Apr 29.
[20] Wallace VC, Segerdahl AR, Lambert DM, Vandevoorde S, Blackbeard J, Pheby T, Hasnie F, Rice AS. The effect of the palmitoylethanolamide analogue, palmitoylallylamide (L-29) on pain behaviour in rodent models of neuropathy. Br J Pharmacol. 2007 Aug;151(7):1117-28. Epub 2007 Jun 11.
[21] LoVerme J, Russo R, La Rana G, Fu J, Farthing J, Mattace-Raso G, Meli R, Hohmann A, Calignano A, Piomelli D. Rapid broad-spectrum analgesia through activation of peroxisome proliferator-activated receptor-alpha. J Pharmacol Exp Ther. 2006 Dec;319(3):1051-61. Epub 2006 Sep 22.
[22] Farquhar-Smith WP, Rice AS. Administration of endocannabinoids prevents a referred hyperalgesia associated with inflammation of the urinary bladder. Anesthesiology. 2001 Mar;94(3):507-13; discussion 6A.
[23] Jaggar SI, Hasnie FS, Sellaturay S, Rice AS. The anti-hyperalgesic actions of the cannabinoid anandamide and the putative CB2 receptor agonist palmitoylethanolamide in visceral and somatic inflammatory pain. Pain. 1998 May;76(1-2):189-99.
[24] De Filippis D, Luongo L, Cipriano M, Palazzo E, Cinelli MP, de Novellis V, Maione S, Iuvone T. Palmitoylethanolamide reduces granuloma-induced hyperalgesia by modulation of mast cell activation in rats. Mol Pain. 2011 Jan 10;7:3.
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[26] Ford GK, Kieran S, Dolan K, Harhen B, Finn DP. A role for the ventral hippocampal endocannabinoid system in fear-conditioned analgesia and fear responding in the presence of nociceptive tone in rats. Pain. 2011 Nov;152(11):2495-504. doi: 10.1016/j.pain.2011.07.014. Epub 2011 Aug 23.
[27] Ambrosino P, Soldovieri MV, Russo C, Taglialatela M. Activation and desensitization of TRPV1 channels in sensory neurons by the PPAR? agonist palmitoylethanolamide. Br J Pharmacol. 2013 Mar;168(6):1430-44. doi: 10.1111/bph.12029.
[28] González-Hernández A1, Martínez-Lorenzana G, Rodríguez-Jiménez J, Rojas-Piloni G, Condés-Lara M. Intracisternal injection of palmitoylethanolamide inhibits the peripheral nociceptive evoked responses of dorsal horn wide dynamic range neurons. J Neural Transm. 2015 Mar;122(3):369-74. doi: 10.1007/s00702-014-1255-6. Epub 2014 Jun 12.
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[30] Keppel Hesselink JM, Kopsky DJ. Treatment of chronic regional pain syndrome type 1 with palmitoylethanolamide and topical ketamine cream: modulation of nonneuronal cells. J Pain Res. 2013 Mar 21;6:239-45. doi: 10.2147/JPR.S42417. Print 2013.
[31] 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).
[32] Hugger A, Schindler HJ, Türp JC, Hugger S. [Pharmacological therapy of temporomandibular joint pain]. Z Evid Fortbild Qual Gesundhwes. 2013;107(4-5):302-8. doi: 10.1016/j.zefq.2012.12.003. Epub 2013 Jan 11.
[33] 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. European Journal of Pain Supplements, Volume 4, Issue 1, May 2010, Page 77. DOI: 10.1016/S1754-3207(10)70270-4
[34] Matias I, Wang JW, Moriello AS, Nieves A, Woodward DF, Di Marzo V. Changes in endocannabinoid and palmitoylethanolamide levels in eye tissues of patients with diabetic retinopathy and age-related macular degeneration. Prostaglandins Leukot Essent Fatty Acids. 2006 Dec;75(6):413-8. Epub 2006 Oct 2.
[35] Schifiliti C, et al. Efficacy of palmitoylethanolamide in pain and neuropathic symptoms in diabetic patients Presentation at IV congress of European Schock society, Taormina, 2011.
[36] Matias I, Wang JW, Moriello AS, Nieves A, Woodward DF, Di Marzo V. Changes in endocannabinoid and palmitoylethanolamide levels in eye tissues of patients with diabetic retinopathy and age-related macular degeneration. Prostaglandins Leukot Essent Fatty Acids. 2006 Dec;75(6):413-8. Epub 2006 Oct 2.
[37] Adiletta S et al. Pregabalin and Palmitoylethanolamide in diabetic neuropathic pain: an randomized clinical trial. Presented at the 34th AISD meeting, 2011, Riccione.
[38] Donvito G, Bettoni I, Comelli F, Colombo A, Costa B1. Palmitoylethanolamide relieves pain and preserves pancreatic islet cells in a murine model of diabetes. CNS Neurol Disord Drug Targets. 2015;14(4):452-62.
[39] Blanco I, Béritze N, Argüelles M, Cárcaba V, Fernández F, Janciauskiene S, Oikonomopoulou K, de Serres FJ, Fernández-Bustillo E, Hollenberg MD. Abnormal overexpression of mastocytes in skin biopsies of
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[40] 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.
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[42] Desio, P et al. Efficacy of palmitoylethanolamide and oxycodon in patients with low back pain. Anesthesia and medicina critica (AMC) 2011, 2: 62-71.
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[44] Dominguez CM et al. Palmitoylethanolamide on standard care in lumbosciatic pain, a pragmatic trial. Paper presented at 8th National Congress of the Sociedad Española del Dolor.
[45] Canteri L et al. Reduction of analgesics in patients suffering from lumbosciatic pain, treated with palmitoylethanolamide. Dolor 2010 25:227-234.
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[47] Desio P, Combination of pregabalin and palmitoylethanolamide (PEA) for neuropathic pain treatment. Pathos 2010;17:9-14.
[48] Sarchielli P, Pini LA, Coppola F, Rossi C, Baldi A, Mancini ML, Calabresi P. Endocannabinoids in chronic migraine: CSF findings suggest a system failure. Neuropsychopharmacology. 2007 Jun;32(6):1384-90. Epub 2006 Nov 22.
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[51] Zhang XC, Strassman AM, Burstein R, Levy D. Sensitization and activation of intracranial meningeal nociceptors by mast cell mediators. J Pharmacol Exp Ther. 2007 Aug;322(2):806-12. Epub 2007 May 4.
[52] Wallace VC, Segerdahl AR, Lambert DM, Vandevoorde S, Blackbeard J, Pheby T, Hasnie F, Rice AS. The effect of the palmitoylethanolamide analogue, palmitoylallylamide (L-29) on pain behaviour in rodent models of neuropathy. Br J Pharmacol. 2007 Aug;151(7):1117-28. Epub 2007 Jun 11.
[53] Desio P, Combination of pregabalin and palmitoylethanolamide (PEA) for neuropathic pain treatment. Pathos 2010;17:9-14.
[54] Starowicz K, Przewlocka B. Modulation of neuropathic-pain-related behaviour by the spinal endocannabinoid/endovanilloid system. Philos Trans R Soc Lond B Biol Sci. 2012 Dec 5;367(1607):3286-99. doi: 10.1098/rstb.2011.0392.
[55] Cocito D, Peci E, Ciaramitaro P, Merola A, Lopiano L. Short-term efficacy of ultramicronized palmitoylethanolamide in peripheral neuropathic pain. Pain Res Treat. 2014;2014:854560. doi: 10.1155/2014/854560. Epub 2014 May 20.
[56] Skaper SD, Facci L, Fusco M, Della Valle MF, Zusso M, Costa B, Giusti P. Palmitoylethanolamide, a naturally occurring disease-modifying agent in neuropathic pain. Inflammopharmacology. 2014 Apr;22(2):79-94. doi: 10.1007/s10787-013-0191-7. Epub 2013 Nov 1.
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[69] Correa F, Hernangómez-Herrero M, Mestre L, Lorí­a F, Docagne F, Guaza C. The endocannabinoid anandamide downregulates IL-23 and IL-12 subunits in a viral model of multiple sclerosis: evidence for a cross-talk between IL-12p70/IL-23 axis and IL-10 in microglial cells. Brain Behav Immun. 2011 May;25(4):736-49. Epub 2011 Feb 16.
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[79] Farquhar-Smith WP, Rice AS. Administration of endocannabinoids prevents a referred hyperalgesia associated with inflammation of the urinary bladder. Anesthesiology. 2001 Mar;94(3):507-13; discussion 6A.
[80] Jaggar SI, Hasnie FS, Sellaturay S, Rice AS. The anti-hyperalgesic actions of the cannabinoid anandamide and the putative CB2 receptor agonist palmitoylethanolamide in visceral and somatic inflammatory pain. Pain. 1998 May;76(1-2):189-99.
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[87] Pessina F, Capasso R, Borrelli F, Aveta T, Buono L, Valacchi G, Fiorenzani P, Di Marzo V, Orlando P, Izzo AA. Protective effect of palmitoylethanolamide in a rat model of cystitis. J Urol. 2015 Apr;193(4):1401-8. doi: 10.1016/j.juro.2014.11.083. Epub 2014 Nov 18.
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[90] 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. Epub 2010 Feb 21.
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