Skip to main content
SpringerLink
Log in

The peritoneum—an important factor for pathogenesis and pain generation in endometriosis

  • Review
  • Published:
Journal of Molecular Medicine Aims and scope Submit manuscript

Abstract

Endometriosis (EM) is an oestrogen-dependent disease affecting 10–15 % of women during reproductive age. It is characterised by the presence of endometrial glands, stromal- and smooth muscle-like cells outside of the uterine cavity. Fifty to sixty per cent of women and teenage girls with pelvic pain suffer from EM. EM causes disability and compromises the quality of life in women and young girls significantly. Pain generation in EM is an intricate interplay of several factors such as the endometriotic lesions themselves and the pain-mediating substances, nerve fibres and cytokine-releasing immune cells such as macrophages. These interactions seem to induce a neurogenic inflammatory process. Recently published data demonstrated an increased peptidergic and decreased noradrenergic nerve fibre density in peritoneal lesions. These data could be substantiated by in vitro analyses demonstrating that the peritoneal fluids of patients suffering from EM induced an enhanced sprouting of sensory neurites from chicken dorsal root ganglia and decreased neurite outgrowth from sympathetic ganglia. These findings might be directly involved in the perpetuation of inflammation and pain. Furthermore, the evidence of EM-associated smooth muscle-like cells seems another important factor in pain generation. The peritoneal endometriotic lesion leads to reactions in the surrounding tissue and, therefore, is larger than generally believed. The identification of EM-associated nerve fibres and smooth muscle-like cells fuel discussions on the mechanisms of pain generation in EM, and may present new targets for innovative treatments.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Cramer DW, Missmer SA (2002) The epidemiology of endometriosis. Ann N Y Acad Sci 955:11–22, discussion 34–16, 396–406

    Article  PubMed  Google Scholar 

  2. Milingos S, Protopapas A, Drakakis P, Liapi A, Loutradis D, Kallipolitis G, Milingos D, Michalas S (2003) Laparoscopic management of patients with endometriosis and chronic pelvic pain. Ann N Y Acad Sci 997:269–273

    Article  PubMed  Google Scholar 

  3. Sepulcri Rde P, do Amaral VF (2009) Depressive symptoms, anxiety, and quality of life in women with pelvic endometriosis. Eur J Obstet Gynecol Reprod Biol 142:53–56

    Article  PubMed  Google Scholar 

  4. Fedele L, Bianchi S, Bocciolone L, Di Nola G, Parazzini F (1992) Pain symptoms associated with endometriosis. Obstet Gynecol 79:767–769

    CAS  PubMed  Google Scholar 

  5. Gruppo Italiano per lo Studio dE (2001) Relationship between stage, site and morphological characteristics of pelvic endometriosis and pain. Hum Reprod 16:2668–2671

    Article  Google Scholar 

  6. Vercellini P, Trespidi L, De Giorgi O, Cortesi I, Parazzini F, Crosignani PG (1996) Endometriosis and pelvic pain: relation to disease stage and localization. Fertil Steril 65:299–304

    CAS  PubMed  Google Scholar 

  7. Fauconnier A, Chapron C (2005) Endometriosis and pelvic pain: epidemiological evidence of the relationship and implications. Hum Reprod Update 11:595–606

    Article  CAS  PubMed  Google Scholar 

  8. Fauconnier A, Chapron C, Dubuisson JB, Vieira M, Dousset B, Breart G (2002) Relation between pain symptoms and the anatomic location of deep infiltrating endometriosis. Fertil Steril 78:719–726

    Article  PubMed  Google Scholar 

  9. Koninckx PR, Meuleman C, Demeyere S, Lesaffre E, Cornillie FJ (1991) Suggestive evidence that pelvic endometriosis is a progressive disease, whereas deeply infiltrating endometriosis is associated with pelvic pain. Fertil Steril 55:759–765

    CAS  PubMed  Google Scholar 

  10. Parker JD, Leondires M, Sinaii N, Premkumar A, Nieman LK, Stratton P (2006) Persistence of dysmenorrhea and nonmenstrual pain after optimal endometriosis surgery may indicate adenomyosis. Fertil Steril 86:711–715

    Article  PubMed  Google Scholar 

  11. Vercellini P (1997) Endometriosis: what a pain it is. Semin Reprod Endocrinol 15:251–261

    Article  CAS  PubMed  Google Scholar 

  12. Chapron C, Fauconnier A, Dubuisson JB, Barakat H, Vieira M, Breart G (2003) Deep infiltrating endometriosis: relation between severity of dysmenorrhoea and extent of disease. Hum Reprod 18:760–766

    Article  PubMed  Google Scholar 

  13. Perper MM, Nezhat F, Goldstein H, Nezhat CH, Nezhat C (1995) Dysmenorrhea is related to the number of implants in endometriosis patients. Fertil Steril 63:500–503

    CAS  PubMed  Google Scholar 

  14. Vernon MW, Beard JS, Graves K, Wilson EA (1986) Classification of endometriotic implants by morphologic appearance and capacity to synthesize prostaglandin F. Fertil Steril 46:801–806

    CAS  PubMed  Google Scholar 

  15. Drake TS, O'Brien WF, Ramwell PW, Metz SA (1981) Peritoneal fluid thromboxane B2 and 6-keto-prostaglandin F1 alpha in endometriosis. Am J Obstet Gynecol 140:401–404

    CAS  PubMed  Google Scholar 

  16. Moon YS, Leung PC, Yuen BH, Gomel V (1981) Prostaglandin F in human endometriotic tissue. Am J Obstet Gynecol 141:344–345

    CAS  PubMed  Google Scholar 

  17. Wu MH, Sun HS, Lin CC, Hsiao KY, Chuang PC, Pan HA, Tsai SJ (2002) Distinct mechanisms regulate cyclooxygenase-1 and -2 in peritoneal macrophages of women with and without endometriosis. Mol Hum Reprod 8:1103–1110

    Article  CAS  PubMed  Google Scholar 

  18. Wu MY, Ho HN (2003) The role of cytokines in endometriosis. Am J Reprod Immunol 49:285–296

    Article  PubMed  Google Scholar 

  19. Ota H, Igarashi S, Sasaki M, Tanaka T (2001) Distribution of cyclooxygenase-2 in eutopic and ectopic endometrium in endometriosis and adenomyosis. Hum Reprod 16:561–566

    Article  CAS  PubMed  Google Scholar 

  20. Bulun SE (2009) Endometriosis. N Engl J Med 360:268–279

    Article  CAS  PubMed  Google Scholar 

  21. Garry R (2004) The effectiveness of laparoscopic excision of endometriosis. Curr Opin Obstet Gynecol 16:299–303

    Article  PubMed  Google Scholar 

  22. Teodoro MC, Genovese F, Rubbino G, Palumbo M, Zarbo G (2012) Chronic pelvic pain in patients with endometriosis: results of laparoscopic treatment. Minerva Ginecol 64:9–14

    CAS  PubMed  Google Scholar 

  23. Vercellini P, Somigliana E, Vigano P, Abbiati A, Barbara G, Fedele L (2009) Chronic pelvic pain in women: etiology, pathogenesis and diagnostic approach. Gynecol Endocrinol 25:149–158

    Article  PubMed  Google Scholar 

  24. Lamvu G, Steege JF (2006) The anatomy and neurophysiology of pelvic pain. J Minim Invasive Gynecol 13:516–522

    Article  PubMed  Google Scholar 

  25. Anaf V, Simon P, El Nakadi I, Fayt I, Buxant F, Simonart T, Peny MO, Noel JC (2000) Relationship between endometriotic foci and nerves in rectovaginal endometriotic nodules. Hum Reprod 15:1744–1750

    Article  CAS  PubMed  Google Scholar 

  26. Anaf V, Simon P, El Nakadi I, Fayt I, Simonart T, Buxant F, Noel JC (2002) Hyperalgesia, nerve infiltration and nerve growth factor expression in deep adenomyotic nodules, peritoneal and ovarian endometriosis. Hum Reprod 17:1895–1900

    Article  PubMed  Google Scholar 

  27. Berkley KJ, Dmitrieva N, Curtis KS, Papka RE (2004) Innervation of ectopic endometrium in a rat model of endometriosis. Proc Natl Acad Sci U S A 101:11094–11098

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Zhang X, Yao H, Huang X, Lu B, Xu H, Zhou C (2010) Nerve fibres in ovarian endometriotic lesions in women with ovarian endometriosis. Hum Reprod 25:392–397

    Article  PubMed  Google Scholar 

  29. Arnold J, Barcena de Arellano ML, Ruster C, Vercellino GF, Chiantera V, Schneider A, Mechsner S (2012) Imbalance between sympathetic and sensory innervation in peritoneal endometriosis. Brain Behav Immun 26:132–141

    Article  CAS  PubMed  Google Scholar 

  30. Mechsner S, Schwarz J, Thode J, Loddenkemper C, Salomon DS, Ebert AD (2007) Growth-associated protein 43-positive sensory nerve fibers accompanied by immature vessels are located in or near peritoneal endometriotic lesions. Fertil Steril 88:581–587

    Article  PubMed  Google Scholar 

  31. Tokushige N, Markham R, Russell P, Fraser IS (2006) Nerve fibres in peritoneal endometriosis. Hum Reprod 21:3001–3007

    Article  CAS  PubMed  Google Scholar 

  32. Arnold J, Vercellino GF, Chiantera V, Schneider A, Mechsner S, Barcena de Arellano ML (2013) Neuroimmunomodulatory alterations in non-lesional peritoneum close to peritoneal endometriosis. Neuroimmunomodulation 20:9–18

    Article  CAS  PubMed  Google Scholar 

  33. Tran LV, Tokushige N, Berbic M, Markham R, Fraser IS (2009) Macrophages and nerve fibres in peritoneal endometriosis. Hum Reprod 24:835–841

    Article  CAS  PubMed  Google Scholar 

  34. Barcena de Arellano ML, Arnold J, Lang H, Vercellino GF, Chiantera V, Schneider A, Mechsner S (2014) Evidence of neurotrophic events due to peritoneal endometriotic lesions. Cytokine (in press)

  35. Barcena de Arellano ML, Arnold J, Vercellino F, Chiantera V, Schneider A, Mechsner S (2011) Overexpression of nerve growth factor in peritoneal fluid from women with endometriosis may promote neurite outgrowth in endometriotic lesions. Fertil Steril 95:1123–1126

    Article  CAS  PubMed  Google Scholar 

  36. Barcena de Arellano ML, Arnold J, Vercellino GF, Chiantera V, Ebert AD, Schneider A, Mechsner S (2011) Influence of nerve growth factor in endometriosis-associated symptoms. Reprod Sci 18:1202–1210

    Article  CAS  PubMed  Google Scholar 

  37. Nothnick WB (2001) Treating endometriosis as an autoimmune disease. Fertil Steril 76:223–231

    Article  CAS  PubMed  Google Scholar 

  38. Badaway SZ, Cuenca V, Freliech H, Stefanu C (1990) Endometrial antibodies in serum and peritoneal fluid of infertile patients with and without endometriosis. Fertil Steril 53:930–932

    CAS  PubMed  Google Scholar 

  39. Matarese G, De Placido G, Nikas Y, Alviggi C (2003) Pathogenesis of endometriosis: natural immunity dysfunction or autoimmune disease? Trends Mol Med 9:223–228

    Article  CAS  PubMed  Google Scholar 

  40. Mathur S, Peress MR, Williamson HO, Youmans CD, Maney SA, Garvin AJ, Rust PF, Fudenberg HH (1982) Autoimmunity to endometrium and ovary in endometriosis. Clin Exp Immunol 50:259–266

    CAS  PubMed Central  PubMed  Google Scholar 

  41. Chan OT, Madaio MP, Shlomchik MJ (1999) The central and multiple roles of B cells in lupus pathogenesis. Immunol Rev 169:107–121

    Article  CAS  PubMed  Google Scholar 

  42. Levine JD, Collier DH, Basbaum AI, Moskowitz MA, Helms CA (1985) Hypothesis: the nervous system may contribute to the pathophysiology of rheumatoid arthritis. J Rheumatol 12:406–411

    CAS  PubMed  Google Scholar 

  43. Nance DM, Sanders VM (2007) Autonomic innervation and regulation of the immune system (1987–2007). Brain Behav Immun 21:736–745

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  44. Sanders VM, Kasprowicz DJ, Kohm AP, Swanson MA (2001) Neurotransmitter receptors on lymphocytes and other lymphoid cells2. Academic Press, San Diego, CA

    Google Scholar 

  45. Baerwald C, Graefe C, von Wichert P, Krause A (1992) Decreased density of beta-adrenergic receptors on peripheral blood mononuclear cells in patients with rheumatoid arthritis. J Rheumatol 19:204–210

    CAS  PubMed  Google Scholar 

  46. Heijnen CJ, Rouppe van der Voort C, Wulffraat N, van der Net J, Kuis W, Kavelaars A (1996) Functional alpha 1-adrenergic receptors on leukocytes of patients with polyarticular juvenile rheumatoid arthritis. J Neuroimmunol 71:223–226

    Article  CAS  PubMed  Google Scholar 

  47. Kohm AP, Sanders VM (2000) Norepinephrine: a messenger from the brain to the immune system. Immunol Today 21:539–542

    Article  CAS  PubMed  Google Scholar 

  48. Straub RH (2007) Autoimmune disease and innervation. Brain Behav Immun 21:528–534

    Article  CAS  PubMed  Google Scholar 

  49. Ader R (2007), 4th edn.

  50. Alicea C, Belkowski S, Eisenstein TK, Adler MW, Rogers TJ (1996) Inhibition of primary murine macrophage cytokine production in vitro following treatment with the kappa-opioid agonist U50,488H. J Neuroimmunol 64:83–90

    Article  CAS  PubMed  Google Scholar 

  51. Bouma MG, Stad RK, van den Wildenberg FA, Buurman WA (1994) Differential regulatory effects of adenosine on cytokine release by activated human monocytes. J Immunol 153:4159–4168

    CAS  PubMed  Google Scholar 

  52. Spengler RN, Chensue SW, Giacherio DA, Blenk N, Kunkel SL (1994) Endogenous norepinephrine regulates tumor necrosis factor-alpha production from macrophages in vitro. J Immunol 152:3024–3031

    CAS  PubMed  Google Scholar 

  53. Kavelaars A, Broeke D, Jeurissen F, Kardux J, Meijer A, Franklin R, Gelfand EW, Heijnen CJ (1994) Activation of human monocytes via a non-neurokinin substance P receptor that is coupled to Gi protein, calcium, phospholipase D, MAP kinase, and IL-6 production. J Immunol 153:3691–3699

    CAS  PubMed  Google Scholar 

  54. Lotz M, Vaughan JH, Carson DA (1988) Effect of neuropeptides on production of inflammatory cytokines by human monocytes. Science 241:1218–1221

    Article  CAS  PubMed  Google Scholar 

  55. Serra MC, Calzetti F, Ceska M, Cassatella MA (1994) Effect of substance P on superoxide anion and IL-8 production by human PMNL. Immunology 82:63–69

    CAS  PubMed Central  PubMed  Google Scholar 

  56. Jancsó N, Jancsó-Gabor A, Szolcsányi J (1967) Direct evidence for neurogenic inflammation and its prevention by denervation and by pretreatment with capsaicin. Br J Pharmacol Chemother 31:138–151

    Article  PubMed Central  PubMed  Google Scholar 

  57. Levine JD, Clark R, Devor M, Helms C, Moskowitz MA, Basbaum AI (1984) Intraneuronal substance P contributes to the severity of experimental arthritis. Science 226:547–549

    Article  CAS  PubMed  Google Scholar 

  58. Harle P, Mobius D, Carr DJ, Scholmerich J, Straub RH (2005) An opposing time-dependent immune-modulating effect of the sympathetic nervous system conferred by altering the cytokine profile in the local lymph nodes and spleen of mice with type II collagen-induced arthritis. Arthritis Rheum 52:1305–1313

    Article  PubMed  Google Scholar 

  59. Mapp PI, Walsh DA, Garrett NE, Kidd BL, Cruwys SC, Polak JM, Blake DR (1994) Effect of three animal models of inflammation on nerve fibres in the synovium. Ann Rheum Dis 53:240–246

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  60. Ahmed M, Bjurholm A, Schultzberg M, Theodorsson E, Kreicbergs A (1995) Increased levels of substance P and calcitonin gene-related peptide in rat adjuvant arthritis. A combined immunohistochemical and radioimmunoassay analysis. Arthritis Rheum 38:699–709

    Article  CAS  PubMed  Google Scholar 

  61. Goode T, O'Connell J, Anton P, Wong H, Reeve J, O'Sullivan GC, Collins JK, Shanahan F (2000) Neurokinin-1 receptor expression in inflammatory bowel disease: molecular quantitation and localisation. Gut 47:387–396

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  62. Miller LE, Weidler C, Falk W, Angele P, Schaumburger J, Scholmerich J, Straub RH (2004) Increased prevalence of semaphorin 3C, a repellent of sympathetic nerve fibers, in the synovial tissue of patients with rheumatoid arthritis. Arthritis Rheum 50:1156–1163

    Article  CAS  PubMed  Google Scholar 

  63. Chen H, He Z, Tessier-Lavigne M (1998) Axon guidance mechanisms: semaphorins as simultaneous repellents and anti-repellents. Nat Neurosci 1:436–439

    Article  CAS  PubMed  Google Scholar 

  64. Ferrero S, Haas S, Remorgida V, Camerini G, Fulcheri E, Ragni N, Straub RH, Capellino S (2010) Loss of sympathetic nerve fibers in intestinal endometriosis. Fertil Steril 94:2817–2819

    Article  PubMed  Google Scholar 

  65. Mechsner S, Bartley J, Loddenkemper C, Salomon DS, Starzinski-Powitz A, Ebert AD (2005) Oxytocin receptor expression in smooth muscle cells of peritoneal endometriotic lesions and ovarian endometriotic cysts. Fertil Steril 83(Suppl 1):1220–1231

    Article  CAS  PubMed  Google Scholar 

  66. Fukunaga M (2000) Smooth muscle metaplasia in ovarian endometriosis. Histopathology 36:348–352

    Article  CAS  PubMed  Google Scholar 

  67. van Kaam KJ, Schouten JP, Nap AW, Dunselman GA, Groothuis PG (2008) Fibromuscular differentiation in deeply infiltrating endometriosis is a reaction of resident fibroblasts to the presence of ectopic endometrium. Hum Reprod 23:2692–2700

    Article  PubMed  Google Scholar 

  68. Barcena de Arellano ML, Gericke J, Reichelt U, Okuducu AF, Ebert AD, Chiantera V, Schneider A, Mechsner S (2011) Immunohistochemical characterization of endometriosis-associated smooth muscle cells in human peritoneal endometriotic lesions. Hum Reprod 26:2721–2730

    Article  CAS  PubMed  Google Scholar 

  69. Abbott JA, Hawe J, Clayton RD, Garry R (2003) The effects and effectiveness of laparoscopic excision of endometriosis: a prospective study with 2–5 year follow-up. Hum Reprod 18:1922–1927

    Article  CAS  PubMed  Google Scholar 

  70. Vercellini P, Chapron C, De Giorgi O, Consonni D, Frontino G, Crosignani PG (2003) Coagulation or excision of ovarian endometriomas? Am J Obstet Gynecol 188:606–610

    Article  PubMed  Google Scholar 

  71. Jones KD, Haines P, Sutton CJ (2001) Long-term follow-up of a controlled trial of laser laparoscopy for pelvic pain. JSLS 5:111–115

    CAS  PubMed Central  PubMed  Google Scholar 

  72. Sutton CJ, Ewen SP, Whitelaw N, Haines P (1994) Prospective, randomized, double-blind, controlled trial of laser laparoscopy in the treatment of pelvic pain associated with minimal, mild, and moderate endometriosis. Fertil Steril 62:696–700

    CAS  PubMed  Google Scholar 

  73. Jarrell J, Mohindra R, Ross S, Taenzer P, Brant R (2005) Laparoscopy and reported pain among patients with endometriosis. J Obstet Gynaecol Can 27:477–485

    PubMed  Google Scholar 

  74. Yeung P Jr, Sinervo K, Winer W, Albee RB Jr (2011) Complete laparoscopic excision of endometriosis in teenagers: is postoperative hormonal suppression necessary? Fertil Steril 95:1909–1912, 1912 e1901

    Article  PubMed  Google Scholar 

  75. Murphy AA, Green WR, Bobbie D, dela Cruz ZC, Rock JA (1986) Unsuspected endometriosis documented by scanning electron microscopy in visually normal peritoneum. Fertil Steril 46:522–524

    CAS  PubMed  Google Scholar 

  76. Lessey BA, Bushnell GA, Miller SE, Price TA (2011) Focal peritoneal dysfunction and endometriosis: a new theory for pelvic pain. World congress on endometriosis, Montpellier, France, pp. 30

  77. Zoubina EV, Fan Q, Smith PG (1998) Variations in uterine innervation during the estrous cycle in rat. J Comp Neurol 397:561–571

    Article  CAS  PubMed  Google Scholar 

  78. Zoubina EV, Mize AL, Alper RH, Smith PG (2001) Acute and chronic estrogen supplementation decreases uterine sympathetic innervation in ovariectomized adult virgin rats. Histol Histopathol 16:989–996

    CAS  PubMed  Google Scholar 

  79. Attar E, Bulun SE (2006) Aromatase and other steroidogenic genes in endometriosis: translational aspects. Hum Reprod Update 12:49–56

    Article  CAS  PubMed  Google Scholar 

  80. Bulun SE, Imir G, Utsunomiya H, Thung S, Gurates B, Tamura M, Lin Z (2005) Aromatase in endometriosis and uterine leiomyomata. J Steroid Biochem Mol Biol 95:57–62

    Article  CAS  PubMed  Google Scholar 

  81. Kitawaki J, Noguchi T, Amatsu T, Maeda K, Tsukamoto K, Yamamoto T, Fushiki S, Osawa Y, Honjo H (1997) Expression of aromatase cytochrome P450 protein and messenger ribonucleic acid in human endometriotic and adenomyotic tissues but not in normal endometrium. Biol Reprod 57:514–519

    Article  CAS  PubMed  Google Scholar 

  82. Noble LS, Takayama K, Zeitoun KM, Putman JM, Johns DA, Hinshelwood MM, Agarwal VR, Zhao Y, Carr BR, Bulun SE (1997) Prostaglandin E2 stimulates aromatase expression in endometriosis-derived stromal cells. J Clin Endocrinol Metab 82:600–606

    CAS  PubMed  Google Scholar 

  83. Zoubina EV, Smith PG (2001) Sympathetic hyperinnervation of the uterus in the estrogen receptor alpha knock-out mouse. Neuroscience 103:237–244

    Article  CAS  PubMed  Google Scholar 

  84. Chalar C, Richeri A, Viettro L, Chavez-Genaro R, Bianchimano P, Marmol NM, Crutcher K, Burnstock G, Cowen T, Brauer MM (2003) Plasticity in developing rat uterine sensory nerves: the role of NGF and TrkA. Cell Tissue Res 314:191–205

    Article  CAS  PubMed  Google Scholar 

  85. Krizsan-Agbas D, Pedchenko T, Hasan W, Smith PG (2003) Oestrogen regulates sympathetic neurite outgrowth by modulating brain derived neurotrophic factor synthesis and release by the rodent uterus. Eur J Neurosci 18:2760–2768

    Article  CAS  PubMed  Google Scholar 

  86. Kohn J, Aloyz RS, Toma JG, Haak-Frendscho M, Miller FD (1999) Functionally antagonistic interactions between the TrkA and p75 neurotrophin receptors regulate sympathetic neuron growth and target innervation. J Neurosci 19:5393–5408

    CAS  PubMed  Google Scholar 

  87. Bamji SX, Majdan M, Pozniak CD, Belliveau DJ, Aloyz R, Kohn J, Causing CG, Miller FD (1998) The p75 neurotrophin receptor mediates neuronal apoptosis and is essential for naturally occurring sympathetic neuron death. J Cell Biol 140:911–923

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  88. Hasan W, Smith HJ, Ting AY, Smith PG (2005) Estrogen alters trkA and p75 neurotrophin receptor expression within sympathetic neurons. J Neurobiol 65:192–204

    Article  CAS  PubMed  Google Scholar 

  89. Richeri A, Chalar C, Martinez G, Greif G, Bianchimano P, Brauer MM (2012) Estrogen up-regulation of semaphorin 3F correlates with sympathetic denervation of the rat uterus. Auton Neurosci 164:43–50

    Article  Google Scholar 

  90. Straub RH, Lowin T, Klatt S, Wolff C, Rauch L (2011) Increased density of sympathetic nerve fibers in metabolically activated fat tissue surrounding human synovium and mouse lymph nodes in arthritis. Arthritis Rheum 63:3234–3242

    Article  CAS  PubMed  Google Scholar 

  91. Fassold A, Falk W, Anders S, Hirsch T, Mirsky VM, Straub RH (2009) Soluble neuropilin-2, a nerve repellent receptor, is increased in rheumatoid arthritis synovium and aggravates sympathetic fiber repulsion and arthritis. Arthritis Rheum 60:2892–2901

    Article  CAS  PubMed  Google Scholar 

  92. Lepelletier Y, Moura IC, Hadj-Slimane R, Renand A, Fiorentino S, Baude C, Shirvan A, Barzilai A, Hermine O (2006) Immunosuppressive role of semaphorin-3A on T cell proliferation is mediated by inhibition of actin cytoskeleton reorganization. Eur J Immunol 36:1782–1793

    Article  CAS  PubMed  Google Scholar 

  93. Chavez-Genaro R, Crutcher K, Viettro L, Richeri A, Coirolo N, Burnstock G, Cowen T, Brauer MM (2002) Differential effects of oestrogen on developing and mature uterine sympathetic nerves. Cell Tissue Res 308:61–73

    Article  CAS  PubMed  Google Scholar 

  94. Sporrong B, Alm P, Owman C, Sjoberg NO, Thorbert G (1981) Pregnancy is associated with extensive adrenergic nerve degeneration in the uterus. An electronmicroscopic study in the guinea-pig. Neuroscience 6:1119–1126

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgement

The authors thank PD Dr. Andreas Kaufmann for the critical reading and constructive discussion.

Conflict of interest

The authors declare that they have no conflict of interests.

Author information

Authors and Affiliations

  1. Campus Benjamin Franklin, Charité Endometriosis Center, Clinic for Gynecology, Charité University Hospital, Hindenburgdamm 30, Berlin, 12200, Germany

    Maria-Luisa Barcena de Arellano & Sylvia Mechsner

Authors
  1. Maria-Luisa Barcena de Arellano
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sylvia Mechsner
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sylvia Mechsner.

Rights and permissions

Reprints and permissions

About this article

Cite this article

de Arellano, ML.B., Mechsner, S. The peritoneum—an important factor for pathogenesis and pain generation in endometriosis. J Mol Med 92, 595–602 (2014). https://doi.org/10.1007/s00109-014-1135-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00109-014-1135-4

Keywords

Search

Navigation