A review of the available clinical therapies for vulvodynia management and new data implicating proinflammatory mediators in pain elicitation

Abstract

Localized provoked vulvodynia (LPV) is a common, chronic, and disabling condition; patients experience profound pain and a diminished quality of life. The etiologic origins of vulvodynia are poorly understood, yet recent evidence suggests a link to site-specific inflammatory responses. Fibroblasts isolated from the vestibule of LPV patients are sensitive to pro-inflammatory stimuli and copiously produce pain-associated pro-inflammatory mediators (IL‐6 and PGE2). Although LPV is a multifactorial disorder, understanding vulvar inflammation and targeting the inflammatory response should lead to treatment advances, especially for patients exhibiting signs of inflammation. NFkB (already targeted clinically) or other inflammatory components may be suitable therapeutic targets.

Recent advances in understanding provoked vestibulodynia

“…Similar findings were reported when fibroblasts were challenged with live yeast species 51 , and the response was highly predictive of clinically measured pain thresholds. The authors concluded that vulvar tissue of women with and without PVD can be differentiated by the degree of naturally occurring inflammation 52 . They suggested that the vestibule of PVD patients is inherently more sensitive to yeast and that even a subclinical infection may trigger a maladaptive immune response in these fibroblasts.…”

Experimental pain sensitivity in women with vestibulodynia: a pilot study

“…[10][11][12][13] The pain is often described as knife like, burning, irritation or itching, and can be provoked or unprovoked. 10,11 Lifetime prevalence of vulvodynia is 10-15% in the United States and cost of care in the USA has been cited as being greater than $8000 per patient for a 6 month course of treatment.…”

“…10,11 Lifetime prevalence of vulvodynia is 10-15% in the United States and cost of care in the USA has been cited as being greater than $8000 per patient for a 6 month course of treatment. 13 Vulvodynia is thought to be augmented by central sensitization, as evidenced by dynamic vulvar tactile allodynia, body-wide pain threshold reductions, and pain hypervigilance and anxiety.…”

Expression of Estrogen-Related Receptors in Localized Provoked Vulvodynia

“…4,5 Similarly, studies reporting the amount of T cells in LPV specimens have been inconsistent. [5][6][7][8] However, there is evidence of deregulated inflammation in LPV since proinflammatory mediators such as tumor necrosis factor-a and interleukin1-b have been shown to be elevated in women with LPV. 6 In addition, greater numbers of B lymphocytes and mature mucosal IgAplasma cells with a difference in B and T cell arrangement in germinal centers have been detected in vulvar vestibulum of LPV women.…”