Clinical meaning
Vulvodynia is defined as chronic vulvar pain lasting ≥3 months without an identifiable cause. It is classified by the 2015 ISSVD/ISSWSH/IPPS consensus as either localized (vestibulodynia - most common) or generalized, and as provoked (triggered by touch/pressure), unprovoked (spontaneous), or mixed. The molecular pathophysiology involves peripheral and central nervous system sensitization. In the vestibular mucosa of affected patients, there is a significant increase in free nerve fiber density (up to 10-fold increase in intraepithelial nerve fiber density compared to controls), with upregulation of transient receptor potential vanilloid 1 (TRPV1) channels on nociceptive C-fibers. TRPV1 is a ligand-gated non-selective cation channel that responds to capsaicin, protons (pH <6), heat (>43°C), and endogenous lipid mediators (anandamide, 12-HPETE). Upregulated TRPV1 lowers the activation threshold, causing allodynia (pain from normally non-painful stimuli) and hyperalgesia (exaggerated pain response). Mast cell proliferation in the vestibular stroma is another key finding. Activated mast cells release nerve growth factor (NGF), histamine, tryptase, prostaglandins (PGE2), and pro-inflammatory cytokines (IL-6, TNF-α) that promote neuronal sprouting (increased nerve fiber density), nociceptor sensitization, and neurogenic inflammation. NGF binds TrkA receptors on sensory...