(018) Immunohistochemical Characterization of the Innervation of the Vulvar Vestibule in Patients with Suspected Neuroproliferative Vestibulodynia
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
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
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it