Involvement of Heparanase in the Pathogenesis of Localized Vulvodynia

Abstract

Recently, we have shown that vestibular hyperinnervation and the presence of 8 or more mast cells in a 10 x 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.

Stress and Chronic Pelvic Pain

“…Vulvodynia patients have increased mast cell degranulation and infiltration within vestibular biopsies when compared to controls. 191 Specifically, increased mast cell-derived heparanase has been observed in the vestibule of vulvodynia patients, 191 where it serves to degrade the heparin sulfate component of basement membranes and the extracellular matrix as needed for leukocyte infiltration. 192 Mast cell activation increases in post-compared to premenopausal vulvodynia patients, although expression of estrogen receptor α and evidence of neural hyperplasia were similar between groups, 193 suggesting that additional regulatory processes may contribute to the age-related discrepancy.…”

Is Chronic Stress During Childhood Associated with Adult-Onset Vulvodynia?

“…5,22,23,27 A number of scientists have posited that vulvodynia may be the result of an altered immunoinflammatory response. 2,3,[28][29][30][31] If psychosocial risk factors associated with vulvodynia (e.g., childhood abuse) lead to a compromised immune system, this mechanistic pathway would be consistent with the broader, growing literature on the role of chronic stress in generating inflammation. 32,33 Childhood fear of abuse could be conceptualized as a chronic stressor.…”

Inflammation and Chronic Pelvic Pain: A Biological Trigger for Depression in Women?

“…In parallel, the increasing evidence that an appropriate psychotherapeutic regimen can reduce inflammation, depression and pain [106][107][108][109][110][111][112][113][114][115] should encourage a more synergistic treatment approach, by "giving words to pain" to relieve the emotionally intimate burden and its biological correlates, while modulating biological common denominators of the triad (inflammation, depression and CPP) with therapeutic approaches which target a reduction in MC hyperactivity. The final goal is to empower and accelerate the healing process of depression and associated co-morbidities with a womancentered, comprehensive and biologically-based approach.…”