Pain Quality and Tissue Signatures: Histopathological Insights into Vulvodynia and Vulvar Dermatoses

iOBJECTIVE:/i To determine whether qualitative pain characteristics in chronic vulvar discomfort correspond to diagnosis-specific epidermal and dermal histopathological patterns in vulvodynia and vulvar dermatoses. iMETHODS:/i This prospective observational sub-analysis of the DATRIV study included 328 women equally stratified into four groups: normal vulva, impaired asymptomatic vulvar skin, vulvodynia, and vulvar dermatoses (n = 82 per group). Pain quality was assessed using structured clinical interviews and categorized as sharp (fast) or dull (slow) descriptors. Vulvar biopsies underwent blinded histopathological evaluation of epidermal architecture and dermal features, including inflammatory infiltrates, fibrosis, vascularity, adnexal structures, nerve fibers, and mast cells. Associations between pain quality, histopathological findings, and symptom duration were analyzed using proportion tests, pairwise comparisons, and multivariate models. iRESULTS:/i Epidermal architecture was largely preserved in normal vulva, impaired asymptomatic skin, and vulvodynia, whereas epidermal thinning, atrophy, and keratinization disorders were predominantly confined to vulvar dermatoses (p 0.001). Vulvar dermatoses demonstrated a stable inflammatory–fibrotic dermal phenotype characterized by collagen accumulation and hyalinization. In contrast, vulvodynia exhibited a neurovascular–adnexal dermal profile marked by increased nerve fibers, vascular proliferation, sebaceous gland prominence, and increased mast cell density (p 0.001). Sharp pain descriptors were strongly associated with vulvodynia and, within this group, were significantly more prevalent in cases with subtle epidermal abnormalities. Dull descriptors predominated in vulvar dermatoses and corresponded to structural remodeling. In vulvodynia, longer symptom duration was associated with increased dermal inflammation and vascularity, whereas dermal characteristics in vulvar dermatoses remained stable over time. iCONCLUSION:/i Chronic vulvar discomfort demonstrates diagnosis-specific sensory–histopathological coupling. Vulvodynia is characterized by sharp, fast pain qualities linked to a neurocutaneous dermal phenotype, whereas vulvar dermatoses are dominated by dull, slow, inflammation-driven nociception associated with fibrotic remodeling. Integrating structured pain quality assessment with histopathological evaluation enhances diagnostic differentiation and supports mechanism-oriented stratification and individualized management.