Topical resiniferatoxin for the treatment of vestibulodynia: a prospective observational trial

Background Vestibulodynia (VBD) is the most common subtype of vulvodynia and is characterized by persitent, contact-evoked pain localized to the vulvar vestibule. Increasing evidence supports a neuropathic pain mechanism in VBD, including vestibular hyperinnervation, neuroinflammation, and overexpression of the transient receptor potential vanilloid 1 receptor (TRPV1). Despite this, there are no standardized treatment protocols, and available therapies often provide incomplete relief or are limited by systemic side effects. Targeted topical therapies may offer advantages by acting directly on peripheral pain generators. Resiniferatoxin (RTX), a highly potent TRPV1 agonist, induces long-lasting desensitization of nociceptive fibers and may represent a novel therapeutic option for VBD. Objective To evaluate the clinical efficacy, tolerability, and neurophysiological effects of topical RTX cream applied to the vulvar vestibule in women with VBD. Study Design This was a prospective, observational pilot study. Premenopausal women aged ≥18 years with a diagnosis of VBD lasting at least three months were enrolled. Participants applied topical RTX 10 mcg/mL cream to the vulvar vestibule once daily for four weeks using a standardized dosing dispenser. Outcomes included patient-reported pain intensity (visual analog scale for pain and dyspareunia), vestibular cotton swab test scores, levator ani muscle tone, and vestibular current perception thresholds (CPT) at 2000, 250, and 5 Hz. Baseline and 1-month follow-up values were compared using the Wilcoxon signed-rank test and McNemar test, as appropriate. Results Twenty-four women were enrolled (median age 31 years; median VBD duration 66 months). Most participants reported a transient, tolerable burning sensation after RTX application; five women (20.8%) discontinued treatment due to local discomfort. Among participants with complete follow-up, significant improvements were observed at 1 month in provoked vulvar pain and dyspareunia, with median VAS reductions of 2.0 (p=0.01) and 2.5 (p=0.01) points, respectively. Vestibular cotton swab test scores also improved. CPT values increased significantly at 250 Hz and 5 Hz, indicating reduced sensitivity of Aδ and C fibers, while no significant change was observed at 2000 Hz. A reduction in levator ani hypertonicity was observed but did not reach statistical significance. Conclusions Topical RTX was associated with meaningful reductions in vulvar pain and dyspareunia and with objective improvements in vestibular nerve fiber sensitivity in women with VBD. These findings support the role of TRPV1-mediated peripheral mechanisms in VBD and suggest that RTX may be a promising targeted therapy. Larger, placebo-controlled trials with longer follow-up are warranted to confirm these preliminary results.