Molecular mechanisms and therapeutic perspectives in vulvodynia: From current evidence to future investigations.

Vulvodynia is defined as chronic vulvar pain persisting for at least 3 months without a clear identifiable cause. It affects 10%-16% of women, and despite its high prevalence and the severity of symptoms, vulvodynia remains significantly understudied. Here, we consolidate and analyze the scientific literature from the past 25 years, addressing vulvodynia from a molecular perspective. Following an overview of the female genital anatomy, we use a top-down approach to examine in depth the key determinants associated with this disease from the macroscopic to the microscopic scale, such as cellular components, microbiota diversity, hormones, cytokines, receptors, and genetic predispositions. We summarize existing and potential therapeutic strategies, highlighting the importance of further research. Key functional aspects, such as the interactions between the nervous system, immune system, and microbiota, remain to be elucidated. Across published studies, immune system dysfunction emerges as the most consistently reported factor and may contribute to disease development and maintenance.