Archives of Gynecology and Obstetrics

, Volume 290, Issue 2, pp 389–393 | Cite as

Vulvodynia and proctodynia treated with topical baclofen 5 % and palmitoylethanolamide

  • Jan M. Keppel HesselinkEmail author
  • David J. Kopsky
  • Nancy L. Sajben
Case Report



The prevalence of idiopathic vulvodynia and proctodynia is high. Pain management with anti-depressants and anti-epileptics may induce undesirable side effects. Therefore, topical baclofen cream and palmitoylethanolamide might be new therapeutic options.


A 33-year-old woman with intractable chronic vulvar and anal pain had to abstain from sexual intercourse and could neither cycle nor sit for more than 5 min. The patient did not respond to standard treatments. We prescribed a combination of topical baclofen 5 % and palmitoylethanolamide 400 mg, three times daily. After 3 months her symptoms decreased more than 50 % and sexual intercourse was possible again without pain.


Topical baclofen and palmitoylethanolamide can be a viable treatment option in chronic vulvodynia and proctodynia.


Baclofen Cream Palmitoylethanolamide Pain Vulvodynia Proctodynia Pelvic Glia 


Conflict of interest



  1. 1.
    Wesselmann U, Burnett AL, Heinberg LJ (1997) The urogenital and rectal pain syndromes. Pain 73(3):269–294PubMedCrossRefGoogle Scholar
  2. 2.
    Wesselmann U, Reich SG (1996) The dynias. Semin Neurol 16(1):63–74. doi: 10.1055/s-2008-1040961 PubMedCrossRefGoogle Scholar
  3. 3.
    Lehman JS, Sciallis GF (2008) Effective use of topical amitriptyline hydrochloride 2.5% and ketamine hydrochloride 0.5% for analgesia in refractory proctodynia. J drugs in derm 7(9):887–889Google Scholar
  4. 4.
    Reed BD, Harlow SD, Sen A, Legocki LJ, Edwards RM, Arato N, Haefner HK (2012) Prevalence and demographic characteristics of vulvodynia in a population-based sample. Am J Obstet Gynecol 206(2):170 e1–e9. doi: 10.1016/j.ajog.2011.08.012 Google Scholar
  5. 5.
    Xie Y, Shi L, Xiong X, Wu E, Veasley C, Dade C (2012) Economic burden and quality of life of vulvodynia in the United States. Curr Med Res Opin 28(4):601–608. doi: 10.1185/03007995.2012.666963 PubMedCrossRefGoogle Scholar
  6. 6.
    Patsatsi A, Vavilis D, Theodoridis TD, Kellartzis D, Sotiriadis D, Tarlatzis BC (2012) Vulvodynia: a case series of a poorly recognized entity. Clin Exp Obstet Gynecol 39(3):330–332PubMedGoogle Scholar
  7. 7.
    Leo RJ, Dewani S (2012) A systematic review of the utility of antidepressant pharmacotherapy in the treatment of vulvodynia pain. J Sex Med 10(10):2497–2505. doi: 10.1111/j.1743-6109.2012.02915.x PubMedGoogle Scholar
  8. 8.
    Leo RJ (2013) A systematic review of the utility of anticonvulsant pharmacotherapy in the treatment of vulvodynia pain. Sex Med 10(8):2000–2008. doi: 10.1111/jsm.12200 CrossRefGoogle Scholar
  9. 9.
    Donders GG, Bellen G (2012) Cream with cutaneous fibroblast lysate for the treatment of provoked vestibulodynia: a double-blind randomized placebo-controlled crossover study. Low Genit Tract Dis 16(4):427–436. doi: 10.1097/LGT.0b013e31825a2274 CrossRefGoogle Scholar
  10. 10.
    Pagano R, Wong S (2012) Use of amitriptyline cream in the management of entry dyspareunia due to provoked vestibulodynia. Low Genit Tract Dis 16(4):394–397. doi: 10.1097/LGT.0b013e3182449bd6 CrossRefGoogle Scholar
  11. 11.
    Goetsch MF (2012) Unprovoked vestibular burning in late estrogen-deprived menopause: a case series. Low Genit Tract Dis 16(4):442–446. doi: 10.1097/LGT.0b013e31825c2d28 CrossRefGoogle Scholar
  12. 12.
    Alexander GM, Perreault MJ, Reichenberger ER, Schwartzman RJ (2007) Changes in immune and glial markers in the CSF of patients with complex regional pain syndrome. Brain Behav Immun 21(5):668–676. doi: 10.1016/j.bbi.2006.10.009 PubMedCrossRefGoogle Scholar
  13. 13.
    Nickel JC, Tripp DA, Pontari M, Moldwin R, Mayer R, Carr LK, Doggweiler R, Yang CC, Mishra N, Nordling J (2010) Psychosocial phenotyping in women with interstitial cystitis/painful bladder syndrome: a case control study. Urology 183(1):167–172. doi: 10.1016/j.juro.2009.08.133 CrossRefGoogle Scholar
  14. 14.
    Nickel JC, Tripp DA, Pontari M, Moldwin R, Mayer R, Carr LK, Doggweiler R, Yang CC, Mishra N, Nordling J (2010) Interstitial cystitis/painful bladder syndrome and associated medical conditions with an emphasis on irritable bowel syndrome, fibromyalgia and chronic fatigue syndrome. Urology 184(4):1358–1363. doi: 10.1016/j.juro.2010.06.005 CrossRefGoogle Scholar
  15. 15.
    Gur A, Oktayoglu P (2008) Status of immune mediators in fibromyalgia. Curr Pain Headache Rep 12(3):175–181PubMedCrossRefGoogle Scholar
  16. 16.
    Kadetoff D, Lampa J, Westman M, Andersson M, Kosek E (2012) Evidence of central inflammation in fibromyalgia-increased cerebrospinal fluid interleukin-8 levels. J Neuroimmunol 242(1–2):33–38. doi: 10.1016/j.jneuroim.2011.10.013 PubMedCrossRefGoogle Scholar
  17. 17.
    Ji RR, Berta T, Nedergaard M (2013) Glia and pain: is chronic pain a gliopathy? Pain. doi: 10.1016/j.pain.2013.06.022 PubMedCentralGoogle Scholar
  18. 18.
    Vollmer-Conna U, Lloyd A, Hickie I, Wakefield D (1998) Chronic fatigue syndrome: an immunological perspective. Aust NZ J psychiatry 32(4):523–527CrossRefGoogle Scholar
  19. 19.
    Stringer EA, Baker KS, Carroll IR, Montoya JG, Chu L, Maecker HT, Younger JW (2013) Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity in chronic fatigue syndrome: evidence of inflammatory pathology. Trans Med 11:93. doi: 10.1186/1479-5876-11-93 CrossRefGoogle Scholar
  20. 20.
    Bornstein J, Tuma R, Farajun Y, Azran A, Zarfati D (2010) Topical nifedipine for the treatment of localized provoked vulvodynia: a placebo-controlled study. J pain 11(12):1403–1409. doi: 10.1016/j.jpain.2010.03.016 PubMedCrossRefGoogle Scholar
  21. 21.
    Walsh KE, Berman JR, Berman LA, Vierregger K (2002) Safety and efficacy of topical nitroglycerin for treatment of vulvar pain in women with vulvodynia: a pilot study. JGSM 5(4):21–27PubMedGoogle Scholar
  22. 22.
    Kopsky DJ, Keppel Hesselink JM (2012) High doses of topical amitriptyline in neuropathic pain: two cases and literature review. Pain pract 12(2):148–153. doi: 10.1111/j.1533-2500.2011.00477.x PubMedCrossRefGoogle Scholar
  23. 23.
    Keppel Hesselink JM, Kopsky DJ (2013) Treatment of chronic regional pain syndrome type 1 with palmitoylethanolamide and topical ketamine cream: modulation of nonneuronal cells. Pain Res 6:239–245. doi: 10.2147/JPR.S42417 Google Scholar
  24. 24.
    Kopsky DJ, Keppel Hesselink JM (2013) Neuropathic pain due to acromegaly, treated with topical baclofen cream. J Pain Symptom Manage (In Press)Google Scholar
  25. 25.
    Barton DL, Wos EJ, Qin R, Mattar BI, Green NB, Lanier KS, Bearden JD 3rd, Kugler JW, Hoff KL, Reddy PS, Rowland KM Jr, Riepl M, Christensen B, Loprinzi CL (2011) A double-blind, placebo-controlled trial of a topical treatment for chemotherapy-induced peripheral neuropathy: NCCTG trial N06CA. Support care cancer 19(6):833–841. doi: 10.1007/s00520-010-0911-0 PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Nyirjesy P, Lev-Sagie A, Mathew L, Culhane JF (2009) Topical Amitriptyline-Baclofen Cream for the Treatment of Provoked Vestibulodynia. J Lower Genital Tract Disease 13(4):230–236CrossRefGoogle Scholar
  27. 27.
    Whitehead RA, Puil E, Ries CR, Schwarz SK, Wall RA, Cooke JE, Putrenko I, Sallam NA, MacLeod BA (2012) GABA(B) receptor-mediated selective peripheral analgesia by the non-proteinogenic amino acid, isovaline. Neuroscience 213:154–160. doi: 10.1016/j.neuroscience.2012.04.026 PubMedCrossRefGoogle Scholar
  28. 28.
    Reis GM, Duarte ID (2006) Baclofen, an agonist at peripheral GABAB receptors, induces antinociception via activation of TEA-sensitive potassium channels. Br J Pharmacol 149(6):733–739. doi: 10.1038/sj.bjp.0706898 PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Andoh T, Sugiyama K, Fujita M, Iida Y, Nojima H, Saiki I, Kuraishi Y (2008) Pharmacological evaluation of morphine and non-opioid analgesic adjuvants in a mouse model of skin cancer pain. Biol Pharm Bulletin 31(3):520–522CrossRefGoogle Scholar
  30. 30.
    Benke D, Zemoura K, Maier PJ (2012) Modulation of cell surface GABA(B) receptors by desensitization, trafficking and regulated degradation. World Biolo chem 3(4):61–72. doi: 10.4331/wjbc.v3.i4.61 CrossRefGoogle Scholar
  31. 31.
    Roenker NL, Gudelsky GA, Ahlbrand R, Horn PS, Richtand NM (2012) Evidence for involvement of nitric oxide and GABA(B) receptors in MK-801- stimulated release of glutamate in rat prefrontal cortex. Neuropharmacology 63(4):575–581. doi: 10.1016/j.neuropharm.2012.04.032 PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Carlton SM, Hargett GL, Coggeshall RE (1995) Localization and activation of glutamate receptors in unmyelinated axons of rat glabrous skin. Neurosci Lett 197(1):25–28PubMedCrossRefGoogle Scholar
  33. 33.
    Davidson EM, Coggeshall RE, Carlton SM (1997) Peripheral NMDA and non-NMDA glutamate receptors contribute to nociceptive behaviors in the rat formalin test. NeuroReport 8(4):941–946PubMedCrossRefGoogle Scholar
  34. 34.
    Schmid HH (2000) Pathways and mechanisms of N-acylethanolamine biosynthesis: can anandamide be generated selectively? Chem Phys Lipids 108(1–2):71–87PubMedCrossRefGoogle Scholar
  35. 35.
    M. KHJ, T. dB, R. W (2013) Palmitoylethanolamide: a natural body-own anti-inflammatory agent, effective and safe against influenza and common cold. Int J Inflammation (In Press)Google Scholar
  36. 36.
    Keppel Hesselink JM, de Boer T, Witkamp RF (2013) Palmitoylethanolamide: a natural body-own anti-inflammatory agent, effective and safe against influenza and common cold. Int J Inflam 2013:151028. doi: 10.1155/2013/151028 PubMedCentralPubMedGoogle Scholar
  37. 37.
    Bachur NR, Masek K, Melmon KL, Udenfriend S (1965) Fatty acid amides of ethanolamine in mammalian tissues. J Biol Chem 240:1019–1024PubMedGoogle Scholar
  38. 38.
    Keppel Hesselink JM (2013) Evolution in pharmacologic thinking around the natural analgesic palmitoylethanolamide: from nonspecific resistance to PPAR-α agonist and effective nutraceutical. J Pain Res 6:625–634CrossRefGoogle Scholar
  39. 39.
    Scuderi C, Valenza M, Stecca C, Esposito G, Carratu MR, Steardo L (2012) Palmitoylethanolamide exerts neuroprotective effects in mixed neuroglial cultures and organotypic hippocampal slices via peroxisome proliferator-activated receptor-alpha. J Neuroinflammation 9:49. doi: 10.1186/1742-2094-9-21 PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    D’Agostino G, Russo R, Avagliano C, Cristiano C, Meli R, Calignano A (2012) Palmitoylethanolamide protects against the amyloid-beta25-35-induced learning and memory impairment in mice, an experimental model of Alzheimer disease. Neuropsychopharmacology 37(7):1784–1792. doi: 10.1038/npp.2012.25 PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Genovese T, Esposito E, Mazzon E, Di Paola R, Meli R, Bramanti P, Piomelli D, Calignano A, Cuzzocrea S (2008) Effects of palmitoylethanolamide on signaling pathways implicated in the development of spinal cord injury. J Pharm Exp Ther 326(1):12–23. doi: 10.1124/jpet.108.136903 CrossRefGoogle Scholar
  42. 42.
    Truini A, Biasiotta A, Di Stefano G, La Cesa S, Leone C, Cartoni C, Federico V, Petrucci MT, Cruccu G (2011) Palmitoylethanolamide restores myelinated-fibre function in patients with chemotherapy-induced painful neuropathy. CNS Neurol Disord Drug Targ 10(8):916–920CrossRefGoogle Scholar
  43. 43.
    Di Cesare MannelliL, D’Agostino G, Pacini A, Russo R, Zanardelli M, Ghelardini C, Calignano A (2013) Palmitoylethanolamide is a disease-modifying agent in peripheral neuropathy: pain relief and neuroprotection share a PPAR-alpha-mediated mechanism. Mediators Inflamm 2013:328797. doi: 10.1155/2013/328797 Google Scholar
  44. 44.
    Bettoni I, Comelli F, Colombo A, Bonfanti P, Costa B (2013) Non-neuronal cell modulation relieves neuropathic pain: efficacy of the endogenous lipid palmitoylethanolamide. CNS Neurol Disord Drug Targ 12(1):34–44CrossRefGoogle Scholar
  45. 45.
    Esposito E, Cuzzocrea S (2013) Palmitoylethanolamide in homeostatic and traumatic central nervous system injuries. CNS Neurol Disord Drug Targ 12(1):55–61CrossRefGoogle Scholar
  46. 46.
    Luongo L, Guida F, Boccella S, Bellini G, Gatta L, Rossi F, de Novellis V, Maione S (2013) Palmitoylethanolamide reduces formalin-induced neuropathic-like behaviour through spinal glial/microglial phenotypical changes in mice. CNS Neurol Disord Drug Targ 12(1):45–54CrossRefGoogle Scholar
  47. 47.
    Skaper SD, Facci L (2012) Mast cell-glia axis in neuroinflammation and therapeutic potential of the anandamide congener palmitoylethanolamide. Philos Trans R Soc Lond B Biol Sci 367(1607):3312–3325. doi: 10.1098/rstb.2011.0391 PubMedCentralPubMedCrossRefGoogle Scholar
  48. 48.
    Keppel Hesselink JM (2012) New targets in pain, non-neuronal cells, and the role of palmitoylethanolamide. Open Pain J 5:12–23CrossRefGoogle Scholar
  49. 49.
    Keppel Hesselink JM, Hekker TA (2012) Therapeutic utility of palmitoylethanolamide in the treatment of neuropathic pain associated with various pathological conditions: a case series. J Pain Res 5:437–442. doi: 10.2147/JPR.S32143 CrossRefGoogle Scholar
  50. 50.
    Indraccolo U, Barbieri F (2010) Effect of palmitoylethanolamide-polydatin combination on chronic pelvic pain associated with endometriosis: preliminary observations. Eur J Obstet Gynecol Reprod Biol 150(1):76–79. doi: 10.1016/j.ejogrb.2010.01.008 PubMedCrossRefGoogle Scholar
  51. 51.
    Palomba R, De Simone MG, Giovannini A, Bonaccia P, Pinto D Use of palmitotlethanolamide (PEA) + polydatina in the chronic pelvic pain. In: SIAARTI, Parma, Italy, 2010.Google Scholar
  52. 52.
    Calabro RS, Gervasi G, Marino S, Mondo PN, Bramanti P (2010) Misdiagnosed chronic pelvic pain: pudendal neuralgia responding to a novel use of palmitoylethanolamide. Pain Med 11(5):781–784. doi: 10.1111/j.1526-4637.2010.00823.x PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Jan M. Keppel Hesselink
    • 1
    Email author
  • David J. Kopsky
    • 2
  • Nancy L. Sajben
    • 3
  1. 1.Institute for Neuropathic PainBosch en DuinThe Netherlands
  2. 2.Institute for Neuropathic PainAmsterdamThe Netherlands
  3. 3.Scripps Memorial Hospital La JollaLa JollaUSA

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