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The NVA Research Fund was established to provide researchers with the opportunity to gather pilot data on vulvodynia in order to obtain larger-scale funding from institutions such as the National Institutes of Health (click here to read more about the funding available and awards that have been made from the NIH). The Fund has disseminated more than $300,000 for pilot studies on chronic vulvar pain. Typical grants range from $15,000-$25,000. Announcements of funding availability are made by email. If you are interested in receiving these announcements, please email Chris Veasley. Additionally, if you have a current project and are interested in applying for funding, please email Chris Veasley or phone her at 401-398-0830.
To date, NVA grants have been awarded to the following recipients:
Yitzchak Binik, PhD – McGill University
Yitzchak Binik, PhD, professor of psychology at McGill University, was awarded an NVA grant to investigate the relationship between chronic Candida infection and vulvar vestibulitis syndrome (VVS) in an animal model. Many women with VVS report previous recurrent episodes of vulvovaginal Candida infection. This association has led some researchers to propose that chronic Candida infection, in which there is continued irritation of the vulvovaginal mucosa, may lead to the abnormal pain transmission experienced by women with VVS. In the present study, Dr. Binik will evaluate whether chronic Candida infection results in lowered vulvar pain thresholds and reduced mating behavior in mice. In addition, he will determine if the immunological profile associated with chronic Candida infection is similar to the immunological profile in VVS. Dr. Binik’s goal is to use an animal model to pursue novel therapeutic interventions for women with vulvar pain.
Lori Boardman, MD - Brown University, Women and Infants' Hospital
Dr. Boardman was awarded a grant in October 2006 to study the safety of a new treatment for vulvar vestibulitis syndrome. She will use data obtained with NVA funding in an application to the National Institutes of Health in 2007 that will further support the execution of a multi-center, randomized, placebo-controlled clinical trial investigating the efficacy of this treatment.
Jacob Bornstein, MD and Tzipora Falik , MD - Western Galilee Hospital ( Nahariya , Israel )
Drs. Bornstein and Falik were awarded a grant in October 2007 to investigate possible associations between VVS and genes that transcribe proteins found or hypothesized to be involved in the abnormal tissue changes seen in VVS. Specifically, they will study a number of polymorphisms, or variations, of three genes coding for molecules involved in the break down, or degradation, of vestibular mast cells and increased vestibular nerve fiber growth: heparanase, vanilloid receptor-1 (TRPV1), and nerve growth factor (NGF). The subjects for this pilot study will be women suffering from severe vulvar vestibulitis who have experienced pain since their first episode of sexual intercourse. This study is an important exploratory part of a larger-scale study that will help delineate genetic susceptibility to the condition and pave the way for individualized treatment.
David Foster, MD, MPH – University of Rochester
Dr. Foster has been the recipient of two NVA research grants. He first received a grant in 1998 to further his work on the neuro-inflammatory mechanisms of vulvar vestibulitis syndrome. Specifically, Dr. Foster studied the cytokine system that mediates inflammation and the neurokine system that mediates pain. The ultimate goal of this research was to develop specific therapies which would interfere with the cytokine-neurokine pathway and relieve vestibular pain.
A second grant was awarded to Dr. Foster in 2000 to continue his work on the etiology of vulvar vestibulitis. Through cell culture, Dr. Foster found that the fibroblast, a type of cell that produces scar, acts in a peculiar way immunologically in vulvar vestibulitis patients. Dr. Foster proposed to study the mechanism of this difference by testing for genetic differences in cytokine genes as well as melanin genes and relating the genetic findings to observations in cell culture. Dr. Foster’s ultimate goal was to identify certain inflammatory substances released from the relevant fibroblast cells, thereby providing a good target for drug therapy. Dr. Foster’s work with NVA funds enabled him to gather pilot data and receive a large-scale grant from the National Institutes of Health in 2002.
Bernard Harlow, PhD - University of Minnesota School of Public Health
Dr. Harlow was awarded a 5-year grant from the National Institutes of Health in 2000 to study the prevalence of vulvodynia and delineate factors associated with an increased risk of developing the condition (http://www.nva.org/for_medical_professionals/md_harlow.html ). Findings from his ongoing work suggest that vulvodynia may be a consequence of an altered vulvar immuno-inflammatory response mechanism that can occur well before menarche. NVA awarded Dr. Harlow a grant in February 2007 to continue his work in this area. With NVA funds, Dr. Harlow with complete laboratory assessments of vulvar-obtained specimens to determine whether there is a difference in the presence of neurogenic proinflammatory mediators and cytokines, and bactericidal proteins between women with vulvodynia and controls. These laboratory findings coupled with his previous epidemiological data will be used in a grant application to the National Institutes of Health in late 2007 to further explore these hypotheses.
Catherine Leclair, MD and Terry Morgan, MD – Oregon Health & Science University
Drs. Leclair and Morgan were awarded a grant in October 2007 to continue their work investigating the etiology, or underlying mechanism, responsible for increased vestibular nerve fiber density found in women with VVS. They also aim to determine if a mild chronic inflammation involving mast cells plays a role in the initiation and/or perpetuation of the condition. Recent research has shown that women with VVS have a decreased number of estrogen receptors in their vestibular tissue. According to Drs. Leclair and Morgan, one consequence of this decrease may be an up-regulation of another receptor, epidermal growth factor receptor (EGFR), which is a mediator of abnormal nerve cell growth and mast cell development. EGFR shows significant cross-signaling with steroid receptors, such as estrogen receptors, and is also up-regulated by androgen receptor (AR). They hypothesize that abnormal ER down-regulation and/or AR up-regulation may lead to an increase in EGFR expression and the cascade of events culminating in VVS. The long term goal of their research is to determine the underlying mechanisms responsible for the initiation of vestibulitis and develop treatment strategies that will eliminate the need for surgery.
Colin MacNeill, MD - The Milton S. Hershey Medical Center
Dr. MacNeill was awarded a grant to investigate the role of surfactant proteins in the initiation of the inflammatory process in vulvar vestibulitis syndrome (VVS). Surfactant proteins are produced locally in the vaginal and vestibular mucosa and, based on numerous studies in other mucosa, may play an important role in the immune response that protects the vulva and vagina from infection. These proteins are found elsewhere in the body, such as the lung, and studies involving mice that have been genetically altered not to produce these proteins die of infection when housed outside of a sterile environment. Dr. MacNeill hypothesizes that variations in the genes, i.e., polymorphisms, that code for these proteins may be responsible for initiating or maintaining the early inflammatory process in VVS. In this study, he will test this hypothesis by measuring levels of surfactant proteins in vestibular tissue as well as assess eleven different polymorphisms in VVS patients and controls. Ultimately, he will test a novel therapy that modulates the activity of these proteins and postulates that if this process can be detected and treated early, the development of VVS can be stopped. Dr. MacNeill used the data collected with this grant in an application to the National Institutes of Health in early 2007.
Linda McLean, PhD and Caroline Pukall, PhD – Queen's University ( Canada )
Drs. McLean and Pukall were awarded a grant in December 2007 to study pelvic floor muscle function in women with VVS. Specifically, the study's objectives are to determine if, as compared to healthy controls, women with VVS demonstrate: (1) heightened activity of the superficial pelvic floor muscles in response to vestibular pressure and/or stretching of the introitus, or vaginal opening; (2) heightened activity of the deep pelvic floor muscles in response to introital pressure; (3) anticipatory reactions of the superficial and/or deep pelvic floor muscles in response to introital pressure or stretching; and (4) heightened activity of remote muscles (biceps and trapezius muscles) in anticipation of, or in response to, introital pressure or stretching. This study will be the first to investigate whether there are differences in the tonic and reactive contractility of pelvic floor muscles in women with VVS as compared to healthy controls, and to differentiate between superficial and deep pelvic floor muscle responses. The outcome of this work will shed light of the etiology of the condition and guide clinical assessment and management, including the development of new physical therapy techniques and utility of medications, such as neuromuscular transmission blocking agents (e.g., Botox).
Caroline Pukall, PhD - Queen's University
Dr. Pukall was awarded a grant in November 2005 to examine differences between women with primary and secondary vulvar vestibulitis syndrome (VVS). There is a tendency to view all women with VVS as a homogeneous group; however, it has been suggested that differences in etiology, pain characteristics, and treatment outcome exist between these two groups of vestibulitis sufferers. This controlled study will investigate multiple dimensions of pain and its functional effects using various methods, such as standardized self-report measures, a standardized gynecological examination, quantitative sensory testing, and functional magnetic resonance imaging. This study will provide much-needed information regarding different aspects of primary and secondary vestibulitis in order to determine what factors are responsible for initiating and maintaining the pain in primary and secondary vestibulitis. Findings from this study will provide useful information regarding potential etiological factors involved in primary and secondary vestibulitis and may help guide treatment for these women.
Andrea Rapkin, MD and John McDonald, MD – University of California – Los Angeles
Drs. Rapkin and McDonald were awarded a grant in August 2007 to study the efficacy of sequential nerve blocks in women with generalized vulvodynia.
Ursula Wesselmann, MD, PhD – Johns Hopkins University School of Medicine
Dr. Wesselmann was awarded a grant in 1997 to develop a basic science model of vulvodynia. Her aim was to advance the knowledge of the neural mechanisms underlying the disorder in order to develop specific treatment modalities in the future. Dr. Wesselmann’s work with NVA funds enabled her to gather pilot data and receive a large-scale grant from the National Institutes of Health in 2002.
In September 2002 the NVA awarded a second grant to Dr. Wesselmann. The aim of this pilot study is to examine sensory mechanisms contributing to dysesthetic vulvodynia in post-menopausal women and to determine how these sensory mechanisms are affected by hormone replacement therapy. To date, there have been almost no studies on dysesthetic vulvodynia in post-menopausal women. Wesselmann’s study will make important contributions to the understanding of vulvodynia as a function of aging and change in reproductive hormone status. Hopefully, the results of this research will enable women to make an educated decision about hormone replacement therapy with regard to their vulvar pain syndrome.
Steven Witkin, PhD and William Ledger, MD – Cornell University
Steven Witkin, PhD and William Ledger, MD, from Cornell University received their first NVA research grant in 2000. Since then, they have published seven studies reporting their findings of polymorphisms (or small changes) in genes associated with a reduced capacity to terminate inflammation (IL-1ra gene), an increased capacity to initiate inflammatory responses (IL-1beta gene), and a reduced capacity to combat Candida albicans infections (MBL gene). Similarly, they've found decreased circulating levels of the anti-microbial compound, interferon-alpha, increased ex vivo induction of a pro-inflammatory cytokine and decreased production of an anti-inflammatory mediator in women with VVS. They have attempted to differentiate patients on the basis of time of symptom onset, factors associated with onset, history of recurrent yeast infections, degree of vestibular pain and associations with an indicator of an allergic response to seminal fluid. Their findings have verified that more than one biological process is responsible for the initiation of VVS.
The consistent finding that many women have a relative inability to mount an effective anti-microbial immune response coupled with a low capacity to terminate pro-inflammatory immune responses is the basis for their next study funded by NVA in January 2005; Drs. Witkin and Ledger will test the hypothesis that the subset of women with VVS with constant or intermittent vestibular pain and whose pain is too severe to engage in sexual intercourse have a diminished capacity to mount an innate immune response to microorganisms. The doctors hypothesize that a relative inability to prevent the colonization and/or proliferation of microorganisms could lead to a persistent induction of pro-inflammatory mediators and a continual stimulation of nerve fibers in the vestibular region culminating in greatly enhanced sensitivity to touch or pain stimuli. The group's long term objective is to determine the underlying mechanisms that predispose women to develop VVS and to devise methods to end its persistence.
Dr. Witkin was given a third NVA grant in January 2007 to continue his work on the etiology of VVS. Because women with VVS report a variety of events that initially trigger their symptoms, including vulvovaginal infection, childbirth, hormonal alteration and chemical and laser treatment, researchers have been unable to identify the exact etiology of the condition. Since 2000, Dr. Witkin has published several studies showing that some women with VVS have gene alterations (polymorphisms) that make them more susceptible to developing the condition. Women with VVS are more likely to exhibit a reduced capacity to ‘turn-off’ inflammation (IL-1ra gene polymorphism), an increased capacity to initiate inflammation (IL-1beta gene polymorphism) and a reduced capacity to combat Candida albicans infections (MBL gene polymorphism). He now proposes that VVS, regardless of the initial trigger, may be due to vestibular peripheral nerve damage caused by prolonged exposure to reactive oxygen species (ROS). ROS are oxygen-containing molecules that can damage other cells and molecules in the body, i.e., nerve cells; they can be induced by a number of different infectious or non-infectious insults. Specifically, he suggests that ROS persistence, which is known to increase susceptibility to nerve damage and maximize regional sensitivity, may be due to the presence of polymorphisms in genes that either directly inactivate ROS or foster a prolongation of ROS production. With this grant, Dr. Witkin will test this novel and unifying hypothesis by comparing the DNA of women with VVS whose symptoms began after a defined event such as childbirth, vulvovaginal infection or surgery, with those whose symptoms were not associated with any specific event. In addition, he will collect blood samples from these two groups to measure immune responses to the yeast and hyphal forms of Candida. Evidence of a unifying mechanism to explain the diverse clinical observations in women with VVS will lead to an improved ability to identify women at risk for development of this syndrome, the testing of more effective preventative strategies and the formulation of novel treatments.
In December 2007, Drs. Ledger and Witkin received their fourth NVA grant to study a novel treatment for VVS. Their ongoing research has demonstrated that women with VVS can be differentiated into distinct groups based on the presence or absence of polymorphisms, or variations, in specific immune response-related genes, the relative production of pro- and anti-inflammatory cytokines, an allergic response to seminal fluid and whether or not symptoms began with the first act of sexual intercourse. A consistent conclusion based on these findings is that some women with VVS have an increased capacity to initiate inflammation coupled with a relative inability to terminate the inflammatory response. They now propose to apply these novel findings to the treatment of women with VVS. With their current grant, Drs. Ledger and Witkin will determine whether women with VVS will benefit from treatment with Anakinra, an interleukin-1 receptor antagonist currently used to treat rheumatoid arthritis. The second aim their study is to be able to predict those patients who will benefit from this treatment based on their genetic makeup. The doctors hypothesize that some women develop VVS because of a genetic capacity for increased IL-1â production ( CIAS1 gene), and/or deficient IL-1ra production ( IL1RN gene) and/or a defective capacity to inhibit the growth of vulvovaginal microorganisms, or bacteria ( MBL2 gene). Their long-term goal is to discover successful treatments that will provide, at minimum, symptomatic relief and, optimally, a permanent cure for women with VVS.
Additional clinically-focused grants have been awarded to:
Theodore Fellenbaum, MD – Genesys Regional Medical Center
Dr. Fellenbaum was awarded a grant to organize a community-based vulvodynia clinic that also promotes resident physician education. The Genesys Medical Center demonstrated its commitment to establishing a vulvar pain clinic by matching the amount of NVA’s grant. Dr. Fellenbaum is collaborating with members of the Genesys obstetric & gynecologic residency program and the Genesys Medical Education Department.
The goals of this collaboration are:
- to screen, diagnose and treat genital pain disorders of unknown etiology,
- to provide a heretofore absent local rotation in genital pain for Genesys and other hospital Ob/Gyn Resident physicians and medical students,
- to provide educational lectures to other medical disciplines, and
- to establish a means for ongoing educational training and academic research on vulvodynia.
Mary Kendell, MS, WHCNP – George Washington University
Ms. Kendell was awarded a grant to develop a curriculum to train and evaluate ob-gyn residents in the treatment of women with chronic vulvar pain. The educational component of the curriculum includes traditional and web-based learning tools, as well as hands-on training in standardized exam techniques and vulvar colposcopy. To evaluate residents’ competency, the George Washington University School of Medicine utilizes a state-of-the-art Standardized Patient Testing center that allows students and residents to hone their skills. In this controlled environment, faculty can observe and record resident/patient interactions and provide real time feedback to residents on their patient care, medical knowledge, interpersonal skills, professionalism and systems based practice. Ms. Kendell’s initial goal is to develop a successful standardized curriculum that will improve medical residents’ competence and level of comfort in evaluating and treating vulvar pain disorders. Her ultimate goal is to establish a vulvar pain clinic at George Washington University School of Medicine.
Denniz Zolnoun , MD – University of North Carolina
In August 2007, NVA awarded a grant to Dr. Zolnoun to conduct a survey of compounding pharmacies in North Carolina . Given the lack of consensus guidelines for the treatment of vulvodynia, the dependence of many patients suffering the condition on compounded medications and the ongoing struggle that compounding pharmacies face with the government, Dr. Zolnoun and others believe it is critical to gain a better understanding of their practice trends, with particular emphasis on vulvodynia. This knowledge will provide insight into both treatment options for vulvodynia and the impact that current legislation, such as the Safe Drug Compounding Act of 2007, could have on the future of compounding pharmacies. These pharmacies often provide the only source of treatment options for marginalized populations suffering from poorly studied illnesses, such as vulvodynia. Dr. Zolnoun's hypothesis is that many areas of women's health, specifically vulvovaginal disorders, rely heavily on compounding pharmacies and the services they provide. Though this is a commonly acknowledged fact, this survey will provide the objective data needed to empower lobbyists and affect policy change. To that end, she distributed a questionnaire to approximately 500 compounding pharmacies and will analyze the survey data to: (1) demonstrate the importance of compounding pharmacies in the provision of women's health services; (2) establish the prevalence of medications compounded for vulvodynia, 3) identify trends in compounding for vulvodynia; and 4) identify the types and combinations of medications used for the treatment of vulvodynia.
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