title: Growth-associated protein 43-positive sensory nerve fibers accompanied by immature vessels are located in or near peritoneal endometriotic lesions.
abstract: OBJECTIVE
  To investigate the topographical relationship between nerve fibers and peritoneal endometriotic lesions and to determine the origin of endometriosis-associated nerve fibers.
  
  
  METHODS
  Retrospective nonrandomized study.
  
  
  METHODS
  University hospital endometriosis research center.
  
  
  METHODS
  Premenopausal women with histologically confirmed endometriosis were selected (n = 73). Peritoneal endometriotic lesions (n = 106) and unaffected peritoneal biopsies from patients without endometriosis (n = 9) were obtained.
  
  
  METHODS
  Immunohistochemistry was used to study the expression of neurofilament, substance P, smooth muscle actin, von Willebrand factor, growth-associated protein 43, nerve growth factor, and neutrophin-3 in peritoneal endometriotic lesion samples from women with symptomatic endometriosis and in peritoneal samples from women without endometriosis.
  
  
  RESULTS
  Pain-conducting substance-P-positive nerve fibers were found to be directly colocalized with human peritoneal endometriotic lesions in 74.5% of all cases. The endometriosis-associated nerve fibers are accompanied by immature blood vessels within the stroma. Nerve growth factor and neutrophin-3 are expressed by endometriotic cells. Growth-associated protein 43, a marker of neural outgrowth and regeneration, is expressed in endometriosis-associated nerve fibers but not in existing peritoneal nerves.
  
  
  CONCLUSIONS
  The data provide the first evidence of direct contact between sensory nerve fibers and peritoneal endometriotic lesions. This implies that the fibers play an important role in the etiology of endometriosis-associated pelvic pain. Moreover, emerging evidence suggests that peritoneal endometriotic cells exhibit neurotrophic properties.
authors.affiliation: Endometriosis Research Center Berlin, Department of Gynecology, Berlin, Germany.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Mechsner
authors.forename: Jessica
authors.initials: J
authors.lastname: Schwarz
authors.forename: Johanna
authors.initials: J
authors.lastname: Thode
authors.forename: Christoph
authors.initials: C
authors.lastname: Loddenkemper
authors.forename: David S
authors.initials: DS
authors.lastname: Salomon
authors.forename: Andreas D
authors.initials: AD
authors.lastname: Ebert
mesh_terms: D000199:Actins / Q000032:analysis; D000328:Adult; D004715:Endometriosis / Q000473:pathology*; D005260:Female; D019922:GAP-43 Protein / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009130:Muscle, Smooth / Q000473:pathology; D009412:Nerve Fibers / Q000473:pathology*; D017697:Premenopause; D012189:Retrospective Studies; D014841:von Willebrand Factor / Q000032:analysis
chemical_list: D000199:Actins; D019922:GAP-43 Protein; D014841:von Willebrand Factor