Vulvodynia (VD) is a chronic pain disorder affecting up to 15% of women and resulting in substantial impairment in health-related quality-of-life. The treatment of the disorder is hampered by a lack of knowledge regarding its neurobiological basis. The proposed study is based on the general hypothesis that like other persistent pain conditions, VD clinical phenotypes are composed of multiple biological endophenotypes, and that meaningful subgroups can be identified. In the current proposal, we plan to extensively phenotype a large sample of VD patients using functional and structural brain imaging together with genetic, physiological, and biological parameters. We hypothesize that central mechanisms (including alterations in the processing/modulation of interoceptive signals from the external genitals) are important determinants of the clinical presentation, and that differences in these brain signatures could play an important role in treatment responsiveness. Such phenotyping has considerable implications for future drug development. We propose to test this hypothesis by accomplishing three specific aims.
Aim 1 will characterize alterations in multimodal structural brain and connectivity indices in VD. This will be accomplished by applying complex network analysis and machine learning algorithms to compare resting state [RS] functional and structural (grey and white matter) brain imaging in VD patients to 200 age-matched female healthy controls (HC), 200 patients with irritable bowel syndrome (IBS) and 100 patients with interstitial cystitis/painful bladder syndrome which are available from a large brain scan repository at UCLA.
Aim 2 will characterize the connectivity indices in VD and identify the association between structural (grey and white matter) and RS alterations with clinical, behavioral and genetic parameters. This will be accomplished by associating structural and RS functional abnormalities identified in Aim 1 with relevant parameters including: clinical (symptom severity, disease duration, co-morbid pain or psychiatric diagnosis), behavioral (pressure pain thresholds), and biological (candidate gene polymorphisms belonging to clusters of genes related to hypothalamic-pituitary-adrenal [HPA] axis function, pain, inflammatory, catecholamine, and serotonin signaling systems).
Aim 3 will identify VD patient subgroups based on endophenotype clusters by applying advanced mathematical classification techniques to brain, biological, behavioral and clinical endophenotypes. This will be accomplished by combining imaging and other phenotyping data using unsupervised machine learning algorithms and will yield distinct mechanistic subgroups of VD.

Public Health Relevance

Vulvodynia is an understudied, often disabling chronic pain disorder that affects up to 15% of women. Current treatment is limited by lack of knowledge of its causes. In order to improve treatment, we examine the influence of brain structure and functioning genetics, clinical and behavioral factors that may underlie this disorder.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
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Special Emphasis Panel (ZHD1-DSR-L (54))
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Parrott, Estella C
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University of California Los Angeles
Internal Medicine/Medicine
Schools of Medicine
Los Angeles
United States
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Gupta, Arpana; Woodworth, Davis C; Ellingson, Benjamin M et al. (2018) Disease-Related Microstructural Differences in the Brain in Women With Provoked Vestibulodynia. J Pain 19:528.e1-528.e15
Tillisch, Kirsten; Mayer, Emeran A; Gupta, Arpana et al. (2017) Brain Structure and Response to Emotional Stimuli as Related to Gut Microbial Profiles in Healthy Women. Psychosom Med 79:905-913
Gupta, Arpana; Mayer, Emeran A; Acosta, Jonathan R et al. (2017) Early adverse life events are associated with altered brain network architecture in a sex- dependent manner. Neurobiol Stress 7:16-26
Labus, Jennifer S; Naliboff, Bruce; Kilpatrick, Lisa et al. (2016) Pain and Interoception Imaging Network (PAIN): A multimodal, multisite, brain-imaging repository for chronic somatic and visceral pain disorders. Neuroimage 124:1232-7
Gupta, A; Woodworth, D; Rapkin, A et al. (2016) (246) Disease-related microstructural differences in the brain in females with localized provoked vulvodynia. J Pain 17:S36-S37
Gupta, Arpana; Rapkin, Andrea J; Gill, Zafar et al. (2015) Disease-related differences in resting-state networks: a comparison between localized provoked vulvodynia, irritable bowel syndrome, and healthy control subjects. Pain 156:809-19