Involvement of heparanase in the pathogenesis of localized vulvodynia

Jacob Bornstein, Yitzhak Cohen, Doron Zarfati, Shifra Sela, Ella Ophir

Research output: Contribution to journalArticlepeer-review

78 Scopus citations


Recently, we have shown that vestibular hyperinnervation and the presence of 8 or more mast cells in a 10 × 10 microscopic field can be used as diagnostic criteria in localized vulvodynia (vulvar vestibulitis). We have also documented that degranulation of mast cells occurs in these cases. The present study further examines the characteristics of vestibular hyperinnervation and mast cell function in localized vulvodynia to elucidate if the 2 processes-hyperinnervation and mast cell increase and degranulation-are related. We examined vestibular tissue from 7 women aged 18 to 48 with severe localized vulvodynia and from 7 healthy control women. Parallel sections were stained by Giemsa and then immunostained for CD117 and heparanase. Nerve fibers that expressed protein gene product 9.5 were examined. Tissues from women with localized vulvodynia documented a significant increase in vestibular mast cells, subepithelial heparanase activity, and intraepithelial hyperinnervation compared with healthy women. This is the first documentation of heparanase activity in localized vulvodynia. Heparanase, which is degranulated from mast cells, is capable of degrading the vestibular stroma and epithelial basement membrane, thus permitting stromal proliferation and intraepithelial extension of nerve fibers, as seen in the present study. The hyperinnervation has been thought to cause the vestibular hyperesthesia distinctive of localized vulvodynia.

Original languageEnglish
Pages (from-to)136-141
Number of pages6
JournalInternational Journal of Gynecological Pathology
Issue number1
StatePublished - Jan 2008


  • Heparanase
  • Hyperinnervation
  • Immunohistochemistry
  • Localized vulvodynia
  • Vestibulitis


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