(018) Immunohistochemical Characterization of the Innervation of the Vulvar Vestibule in Patients with Suspected Neuroproliferative Vestibulodynia
Notice bibliographique
Résumé
Abstract Introduction Provoked vestibulodynia (PVD) is a chronic pain condition characterized by allodynia localized to the vestibule, the endodermal tissue surrounding the vaginal introitus. 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 known which has led to challenges in adequately managing this condition. Significantly, the microscopic innervation of the vestibule remains incompletely described despite the preliminary data which support the role of peripheral innervation in vestibular pain pathogenesis. Objective To characterize the types and distribution of nerves present in vestibule samples from patients with suspected NPV using a suite of markers of general (protein gene product 9.5, PGP9.5), sensory (calcitonin gene-related peptide, CGRP) and autonomic innervation (vasoactive intestinal polypeptide, VIP and tyrosine hydroxylase, TH) and compare this to cadaveric vestibule tissues; and to investigate whether there is an association between this innervation and NPV etiology using markers of neuroproliferation (nerve growth factor, NGF) and immune activation (c-kit). Methods Archival formalin-fixed, paraffin embedded vestibulectomy samples were obtained from six patients who had previous immunohistochemical staining to confirm NPV diagnosis. All samples were stained with nerve markers PGP9.5 and CGRP, in addition to NGF, and mast cell marker c-kit. A subset of samples was stained with nerve markers TH and VIP to further elucidate specific types of innervation present. Vestibule samples were obtained from female cadaveric donors and were stained with the same suite of antibodies for comparison. All tissues were serially sectioned at 5 μm. Results Nerve fibers immunoreactive for all nerve markers were identified in both patient and cadaveric vestibule. Patient samples were characterized by the proliferation of PGP9.5-positive nerve fibers and c-kit positive mast cells which were identified throughout the tissue stroma, including in proximity to nerve bundles. NGF expression was localized to a subset of nerves including those that demonstrated co-expression of sensory and autonomic nerve markers. Cells immunoreactive for NGF were also observed, including those that showed co-expression with putative mast cells that stained positively for c-kit. Relative to the cadaveric tissues, the patient samples were characterized by increased densities of CGRP, TH, and VIP-immunoreactive fibers which were observed throughout the vestibular mucosa. Some heterogeneity in patterns of innervation was observed between the patient samples, including increased densities of autonomic fibers in one patient as indicated by increased VIP and TH-immunoreactive nerve fibers. Conclusions Our results support the existence of a neuroproliferative subtype of PVD that is characterized by the hyperinnervation of the vestibular mucosa and neuro-immune interactions. This investigation highlights that the proliferation of other nerve fiber types in addition to nociceptive, CGRP-positive fibers, including adrenergic and cholinergic nerve fibers, may be important in PVD etiology in some patients. Heterogeneity in patterns of innervation across individuals with NPV could explain, in part, variability in clinical response to treatment and should be further elucidated in ongoing research efforts. Disclosure No
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».