Vulvodynia: Identification of Potential Relevant Biomarkers
Condition: Vulvodynia
MeSH terms: Vulvodynia
Study type: Observational

Summary: 
      Vulvodynia is a syndrome of unexplained vulvar pain that is frequently accompanied by
      physical disabilities, limitation of daily activities (such as sitting and walking), sexual
      dysfunction and psychologic disability. Originally suggested by McKay, the term "vulvodynia"
      has also been suggested by the International Society for the Study of Vulvar Disease Task
      Force to describe any vulvar pain. The incidence and prevalence of vulvodynia have not been
      well studied. Age distribution for the condition may range from the 20s to the 60s, and it is
      limited almost exclusively to white women. Obstetric and gynecologic history is usually
      unremarkable. Risk-taking sexual behavior is rare, and few patients have a history of
      sexually transmitted diseases. Vulvar pain usually has an acute onset, at times associated
      with episodes of vaginitis or certain therapeutic procedures of the vulva (cryotherapy or
      laser therapy). In most cases, vulvodynia becomes a chronic problem lasting months to years.
      Vulvar pain is frequently described as burning or stinging, or a feeling of rawness or
      irritation.

      Most patients consult several physicians before being diagnosed. Many are treated with
      multiple topical or systemic medications, with minimal relief. In some cases, inappropriate
      therapy may even make the symptoms worse. Since physical findings are few and cultures and
      biopsies are frequently negative, patients may be told that the problem is primarily
      psychologic, thus invalidating their pain and adding to their distress.
    

Detailed description: 
      Sphingosine-1-phosphate (S1P) is a potent anti-apoptotic sphingolipid with potent
      pro-inflammatory actions which are driven in most part by activation of the S1P receptor
      subtype S1PR158. Biologically active S1P is generated by the phosphorylation of sphingosine,
      catalyzed by two sphingosine kinases (SphK1, SphK2). S1P levels are further regulated by its
      dephosphorylation by two phosphatases (SGPP1 and SGPP2) and through degradation by one lyase
      (SGPL1). Once released S1P initiates signaling through a family of five cognate G
      protein-coupled receptors (S1PR1-5), leading to various cellular responses9. S1P signaling
      has important roles in inflammation and cancer. S1P acting via the S1PR1 has been implicated
      in the development of pain of several etiologies as discovered by Salvemini and coworkers and
      subsequently extended by others. FTY720 (fingolimod/Gilenya®) is the first orally available
      agent approved by the FDA for the treatment of relapsing-remitting multiple sclerosis (MS).
      The work by Salvemini's group in providing a mechanistic basis for understanding chronic pain
      through the S1P/S1PR1 axis, provides a promising therapeutic target for the use of agents
      like FTY720 as a novel treatment for pain. Ongoing work by the Salvemini's lab suggests that
      increased expression of S1PR1 in circulating peripheral blood leukocytes (PBLs) may provide a
      relevant biomarker to predict severity and pain induction outcomes as well as predict patient
      responses to anti-S1PR1 approaches.
    

Observational model: Case-Only
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        For patients with vulvodynia-related painwill be offered enrollment into the study. At
        their visit before treatment begins they will have:

        blood drawn ,(about 10ml-two teaspoons) this is research related. The ISSVD (The
        International Society for the Study of Vulvovaginal Disease) classification and diagnostic
        criteria for vulvodynia will be used for inclusion in this study.

        Vulvodynia - Vulvar pain of at least 3 months' duration,

        Descriptors:

          -  Localized (e.g. vestibulodynia, clitorodynia) or Generalized or Mixed (localized and
             generalized)

          -  Provoked (e.g. insertional, contact) or Spontaneous or Mixed (provoked and
             spontaneous)

          -  Onset (primary or secondary)

          -  Temporal pattern (intermittent, persistent, constant, immediate, delayed)
      
Biospecimen description: 
      Peripheral blood leukocytes (PBLs) may provide a relevant biomarker to predict severity and
      pain induction outcomes as well as predict patient responses to anti-S1PR1 approaches.