RESUMEN
BACKGROUND: Provoked vestibulodynia (PVD) is a chronic pain condition characterized by allodynia localized to the vulvar vestibule. The finding of increased densities of nerve fibers in the vestibular mucosa of patients with PVD has led to the identification of a neuroproliferative subtype. The etiology of PVD, including neuroproliferative vestibulodynia (NPV), is not fully understood. The gross and microscopic innervation of the vulvar vestibule remains incompletely described, despite the preliminary data supporting the role of peripheral innervation in PVD. AIM: To characterize the gross anatomic and microscopic innervation of the vulvar vestibule through cadaveric dissection and immunohistochemistry. METHODS: The pudendal nerve and inferior hypogastric plexus (IHP) were dissected using 6 cadaveric donors. Histology and immunohistochemistry were used to confirm patterns of innervation identified gross anatomically. Immunohistochemistry was performed on vestibulectomy specimens obtained from 6 patients diagnosed with NPV and compared with cadaveric vestibular tissues. OUTCOMES: Outcomes included (1) dissection of pelvic innervation and (2) immunohistochemical localization of markers for the following: general innervation protein gene product 9.5 (PGP9.5), sensory innervation (calcitonin gene-related peptide), autonomic innervation (vasoactive intestinal polypeptide, tyrosine hydroxylase), neuroproliferation (nerve growth factor [NGF]), and immune activation (C-kit). RESULTS: Perineal (pudendal) nerve branches were traced to the external wall of the vulvar vestibule. Some anatomic heterogeneity was observed in perineal nerve-branching patterns. Fibers from the IHP were identified in close proximity to the vulvar vestibule. Autonomic and sensory nerve fibers were identified in both patient and cadaveric vulvar vestibule samples. Patient samples were characterized by the proliferation of PGP9.5-positive nerve fibers and C-kit-positive mast cells, which were in proximity to neve bundles and showed coexpression with putative NGF-positive cells. NGF expression was localized to a subset of nerves, including those that demonstrated co-expression of sensory and autonomic nerve markers. Increased densities of autonomic fibers positive for vasoactive intestinal polypeptide and tyrosine hydroxylase were observed in 1 patient sample. CLINICAL TRANSLATION: Heterogeneity in gross and microscopic patterns of innervation could explain variability in clinical response to treatment and should be used to inform future therapeutic interventions. STRENGTHS AND LIMITATIONS: This study used a combination of approaches to elucidate the innervation of the vulvar vestibule, including in NPV. The small sample size is a limitation. CONCLUSION: The vulvar vestibule contains both sensory and autonomic innervation, which may originate from the pudendal nerve and IHP. Our results support the existence of a neuroproliferative subtype that is characterized by the proliferation of sensory and autonomic nerve fibers and neuroimmune interactions.
Asunto(s)
Vulvodinia , Femenino , Humanos , Tirosina 3-Monooxigenasa , Péptido Intestinal Vasoactivo , Factor de Crecimiento Nervioso , CadáverRESUMEN
Pain of the vulvar vestibule, including provoked vestibulodynia, is prevalent among women, yet challenging to treat due to its multifactorial etiology. Recent evidence indicates a neuroproliferative subtype in which hypersensitivity of the vulvar vestibule is due, in part, to hyperinnervation. Detailed knowledge regarding the innervation of the vulvar vestibule is crucial to understanding and treating pain conditions impacting this region. The purpose of this review is to consolidate the current evidence regarding the innervation of the human vulvar vestibule and discuss the implications of this innervation for pathological conditions affecting this tissue. A comprehensive review of the literature was conducted using keywords including vulvar vestibule, innervation, and vestibulodynia to identify articles concerning the innervation of the vulvar vestibule. Fifteen studies published between 1998 and 2017 were reviewed. Evidence from immunohistochemical investigations support that the vulvar vestibule has nociceptive, mechanosensory, sympathetic, and parasympathetic innervation. In pathological samples, hyperinnervation supports the neuroproliferative etiology of provoked vestibulodynia. Additionally, there is some evidence supporting the role of the pudendal nerve in vulvar vestibule innervation, although no cadaveric studies have been reported to date. Progress has been made in our understanding of the innervation of the vulvar vestibule, though further research into the origin of sensory and autonomic innervation of this region is needed. Advancing the knowledge of vulvar vestibule innervation is crucial towards improving our understanding of the function of this tissue, in addition to informing the etiology and management of pain syndromes impacting this region.
Asunto(s)
Vulvodinia , Humanos , Femenino , Vulvodinia/etiología , Vulvodinia/patología , Vulva , DolorAsunto(s)
Consenso , Vulvodinia/terapia , Amitriptilina/uso terapéutico , Analgésicos no Narcóticos/uso terapéutico , Toxinas Botulínicas/uso terapéutico , Terapia Cognitivo-Conductual , Europa (Continente)/epidemiología , Femenino , Gabapentina/uso terapéutico , Humanos , Láseres de Gas/uso terapéutico , Prevalencia , Rehabilitación/métodos , Estimulación Eléctrica Transcutánea del Nervio , Vulva/cirugía , Vulvodinia/epidemiología , Vulvodinia/etiología , Vulvodinia/fisiopatologíaRESUMEN
The study aimed to assess the effects of ospemifene on vulvar vestibule in postmenopausal women with vulvar pain and dyspareunia. Fifty-five postmenopausal women used oral ospemifene 60 mg/d for 60 d. Symptoms of dryness, burning, and dyspareunia were evaluated on a 10 cm visual analog scale. Visual examination of the vulvar vestibule was also conducted. Patients also underwent current perception threshold (CPT) testing obtained from the vulvar vestibule. Fifty-five patients (94.6%) completed the treatment. Hot flashes were the most frequent adverse effects, but this led to a discontinuation of therapy in three patients (5.4%). After therapy, there was a statistically significant decrease from the baseline in the mean scores for dryness, burning, and dyspareunia and reduction of vestibular trophic score (baseline value of 11.2-4.2 after the therapy, p ≤ 002) and cotton swab test scores (2.81 compared with 1.25, p = .001). There was a difference in CPT values for all nerve fibers and more consistent for C fibers (-38% of sensitivity). These results confirm the efficacy of ospemifene on postmenopausal vestibular symptoms and signs; moreover, the drug was effective in normalizing vestibular innervation sensitivity.