More than 50% of all menstruating women suffer from menstruation pain. MDs call this is dysmenorrhea. If the pain arises due to the ovulation, doctors call it primary dysmenorrhea. Secondary dysmenorrhea is also menstrual pain, but this pain is triggered by gynecologic disorders, for instance endometriosis. More than 10% of all women suffers from endometriosis. Endometriosis is a difficult to treat condition where the tissue that normally grows inside of the uterus starts to grow outside of the uterus. Women who have endometriosis can suffer from severe pains during menstruation, but also during intercourse and during bowel movements and urination. The supplement palmitoylethanolamide (and we advise PEA capsules with the quality mark PEA-opt) can often offer relief. PEA capsules used for years under the supervision of MDs and produced via a special patented procedure, with high quality can be identified by the PEA-opt quality marker. The preparations with the PEA-opt® quality mark contain absolutely NO chemical or pharmaceutical excipients (such as magnesium stearate, povidone, sorbitol) or colouring agents (such as titanium dioxide). After all, modern and conscientious consumers do not want any mixes that contain redundant chemical substances or colouring agents, certainly if there are indications that these substances are harmful to our health.

Menstruation pain, endometriosis and neuropathic pain

Neuropathic pain might play a role in endometriosis. Such pain is a real challenging to treat. In many cases endometriosis comes back after treatment.

Current research points out that neuropathic pain mechanisms also play a role in chronic pelvic and abdominal pain and endometriosis. [1] Neuropathic pain means pain due to overactive nerve stimuli. The cells and tissues of the uterus irritates all the little nerves in the pelvis and in the belly, causing abdominal pain, clearly like menstrual pains.

Endometriosis is a nasty problem, because tissues from the uterus start to grow elsewhere, and for instance can also cause sciatic nerve neuropathy (large nerve through the leg) by putting pressure on the nerve. [2] This is rare, but important to keep in mind for gynecologists, due to the possible irreversible damage to the sciatic nerve due to this proliferative endometriosis process. [3][4][5]

Especially when the neuropathic pain in the leg returns or amplifies monthly, possibly in combination with numbness and decrease of strength, neuropathic pain of the sciatic nerve due to endometriosis needs to be checked. [6]

If endometriosis is present in the abdomen or pelvic place, where a lot of nerves can be found, endometriosis can damage other nerves too, and cause again neuropathic pain. [7] Nerves can also grow into the endometriosis tissues and start to cause neuropathic pain. The types of neuropathic pain that can occur with endometriosis are increased sensitivity to pain (hyperalgesia) and pain due to stimuli that are not normally painful (allodynia), for instance intercourse!

Endometriosis pain and inflammatory cells

The identification of neuropathic pain is important in order for an optimal treatment to be offered. [8] On a number of patients, endometriosis turned out to be treatable with the natural pain relieving substance palmitoylethanolamide (PEA).

A higher concentration of mast cells is present in the endometriosis spots, which can cause an inflammatory response and make the nerves more sensitive. [9] [10] This could develop in to neuropathic pain. [11] PEA has an inhibiting effect on the activated mast cells. [12] This way PEA has both an anti-inflammatory as well as a pain-relieving effect on neuropathic pain. [13] PEA inhibits important inflammatory mediators, like TNF-Alpha and IL1 as well as COX-2, making it a potentially important substance in the treatment of a variety of conditions besides endometriosis. [14]

The nerve fibers that neuropathic pain causes are presumably the thin C fibers and autonomic nerve fibers. The neuropathic pain questionnaire, like the DN-4, can help to distinguish if the endometriosis pain is of neuropathic nature or not. The body’s own substance palmitoylethanolamide shows to bring relief for endometriosis pain. [15]

For pain relief and for inhibiting inflammation, most patients choose:

  • PEA capsules produced in the Netherlands by Russell
  • PEA tablets produced in Italy by Epitech

Treatment of Endometriosis pain by palmitoylethanolamide

Patients with a pain score of over 5 (on a scale of 0-10 with 10 being the most pain imaginable) were given a combination preparation of 400mg palmitoylethanolamide and 40mg polydatin twice a day for 90 days.

Pain relief appeared after only one month. As the pelvic pain and pain during intercourse averagely scored the highest among women (around 8), these turned out to be the pains that showed the most effect (to a score of 2 after 90 days). On top of that the women needed to take fewer painkillers. Ultra-sound scans showed a small decrease of endometriosis spots.

Meanwhile thousands of patients with severe pain have been treated with this substance, often with impressive results. PEA shows to be effective for severe back and hernia pain, shingles pain, pain due to pinched nerves like with the carpal tunnel syndrome, chronic jaw pain and diabetes pain, to name a few difficult to treat types of pain. The substance can be taken with other pain killers without any problems, if necessary and has no negative effects on the effectiveness of other medicine. [16] [17] [18] [19] [20] [15] [22] [24] [25] [26] [27] [28]

Because of this, palmitoylethanolamide can safely be used for menstruation pains due to endometriosis.

References on PEA in pelvic pain

[1] Howard FM. | Endometriosis and mechanisms of pelvic pain. | J Minim Invasive Gynecol. | 2009 Sep-Oct;16(5):540-50. doi: 10.1016/j.jmig.2009.06.017.

[2] Murata Y, Ogata S, Ikeda Y, Yamagata M. | An unusual cause of sciatic pain as a result of the dynamic motion of the obturator internus muscle. | Spine J. | 2009 Jun;9(6):e16-8. doi: 10.1016/j.spinee.2009.01.004. Epub 2009 Feb 12.

[3] Mannan K, Altaf F, Maniar S, Tirabosco R, Sinisi M, Carlstedt T. | Cyclical sciatica: endometriosis of the sciatic nerve. | J Bone Joint Surg Br. | 2008 Jan;90(1):98-101.

[4] Possover M, Chiantera V. | Isolated infiltrative endometriosis of the sciatic nerve: a report of three patients. | Fertil Steril. | 2007 Feb;87(2):417.e17-9.

[5] GRANBERRY WM, HENDERSON ED, MILLER RH, FABER JE, DOCKERTY MB. |Endometriosis of the sciatic nerve without evidence of pelvic endometriosis. Report of a case. | Minn Med. | 1959 Dec;42:1794-7.

[6] Zager EL, Pfeifer SM, Brown MJ, Torosian MH, Hackney DB. | Catamenial mononeuropathy and radiculopathy: a treatable neuropathic disorder. | J Neurosurg. |1998 May;88(5):827-30.

[7] Berkley KJ, Rapkin AJ, Papka RE. | The pains of endometriosis. | Science. | 2005 Jun 10;308(5728):1587-9.

[8] Chavez NF, Zweizig SL, Stewart EA. | Neuropathic uterine pain after hysterectomy. A case report. | J Reprod Med. | 2003 Jun;48(6):466-8.

[9] Sugamata M, Ihara T, Uchiide I. | Increase of activated mast cells in human endometriosis. | Am J Reprod Immunol. | 2005 Mar;53(3):120-5.

[10] Konno R, Yamada-Okabe H, Fujiwara H, Uchiide I, Shibahara H, Ohwada M, Ihara T, Sugamata M, Suzuki M. | Role of immunoreactions and mast cells in pathogenesis of human endometriosis–morphologic study and gene expression analysis. | Hum Cell. |2003 Sep;16(3):141-9.

[11] Anaf V, Chapron C, El Nakadi I, De Moor V, Simonart T, Noël JC. | Pain, mast cells, and nerves in peritoneal, ovarian, and deep infiltrating endometriosis. | Fertil Steril. | 2006 Nov;86(5):1336-43. Epub 2006 Sep 27.

[12] 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.

[13] 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.

[14] Hoareau L, Buyse M, Festy F, Ravanan P, Gonthier MP, Matias I, Petrosino S, Tallet F, d’Hellencourt CL, Cesari M, Di Marzo V, Roche R. | Anti-inflammatory effect of palmitoylethanolamide on human adipocytes. | Obesity (Silver Spring). | 2009 Mar;17(3):431-8. doi: 10.1038/oby.2008.591. Epub 2009 Jan 8.

[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] 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

[17] 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.

[18] 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.

[19] 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)

[20] 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.

[21] 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.

[22] 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.

[24] 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.

[25] 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.

[26] 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.

[27] 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.

[28] 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.