Mechanisms of Vulvodynia Involving Dysregulation of Pro-Resolving Lipids

Localized provoked vulvodynia (LPV) is characterized by acute and lasting pain in response to light touch of the vulvar vestibule (area immediately surrounding the vaginal opening), which is associated with a reduction in quality of life. Although women afflicted with LPV experience profound pain that negatively impacts their sexual health, they show no overt signs of disease. The origins of vulvodynia are poorly understood, and no current therapy targets the root of the disease or is completely curative, perhaps save surgical amputation of the affected tissue. The goal of our research is to identify less invasive, ideally topical, therapies.

We have determined that a persistent low level of inflammation, generally undetectable clinically, is a key contributor to vulvodynia. Most recently, we have uncovered evidence pointing to a defect in the ability to resolve this inflammation, which may be the product of alterations in the presence or abundance of the molecules that help resolve inflammation named specialized pro-resolving mediators (SPMs) and the receptors that recognize these SPMs. Exogenous SPM treatment can overcome such defects, reducing inflammatory markers in both tissue culture and mouse models of disease, as well as measures of pain in mice, suggesting SPMs are excellent therapeutic candidates. SPMs are naturally produced by the body through metabolism of omega-3 and omega-6 fatty acids and are safe. Although our work in this area is ongoing, our findings suggest vulvodynia is the product of “two hits.” The first hit involves exaggerated inflammatory signaling, rendering the vestibule hypersensitive to inflammatory stimuli, such that a woman’s own natural flora may elicit a response. We are currently focusing on investigating the second hit, involving dysregulation of the resolution machinery.

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