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 neurons, upregulating TRPV1 and substance P expression through the p38 MAPK signaling pathway. This creates a positive feedback loop: mast cell mediators sensitize nerves → sensitized nerves release substance P and CGRP → these neuropeptides degranulate mast cells → perpetuating chronic neuroinflammation.
Pelvic floor myalgia is present in up to 80% of vulvodynia patients. Chronic guarding and hypertonicity of the levator ani, bulbospongiosus, and ischiocavernosus muscles create myofascial trigger points that contribute to pain through muscle ischemia, lactic acid accumulation, and further peripheral nerve sensitization. Central sensitization develops over time as persistent nociceptive input from the periphery causes neuroplastic changes in the dorsal horn of the spinal cord - increased excitability of wide dynamic range (WDR) neurons, loss of descending inhibitory modulation, and expansion of receptive fields. This manifests clinically as pain spreading beyond the original site and hypersensitivity to non-noxious stimuli.