Evidence map›Paper›PMID 41842953›Full record

ArticleThe Journal of clinical investigation2026

Repeatedly occurring retrograde menstruation intensifies central sensitization driven by neuroinflammation in endometriosis models.

Madeleine E Harvey, Mingxin Shi, Yeongseok Oh, Taylor M Page, Debra A Mitchell, Addie Luo, Ov D Slayden, James A MacLean, Anjali Sharma, Kanako Hayashi

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical investigation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Madeleine E HarveySchool of Molecular Biosciences, Center for Reproductive Biology, Washington State University, Pullman, Washington, USA.
Mingxin ShiSchool of Molecular Biosciences, Center for Reproductive Biology, Washington State University, Pullman, Washington, USA.
Yeongseok OhSchool of Molecular Biosciences, Center for Reproductive Biology, Washington State University, Pullman, Washington, USA.
Taylor M PageSchool of Molecular Biosciences, Center for Reproductive Biology, Washington State University, Pullman, Washington, USA.
Debra A MitchellSchool of Molecular Biosciences, Center for Reproductive Biology, Washington State University, Pullman, Washington, USA.
Addie LuoDivision of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA.
Ov D SlaydenDivision of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA.
James A MacLeanSchool of Molecular Biosciences, Center for Reproductive Biology, Washington State University, Pullman, Washington, USA.
Anjali SharmaDepartment of Chemistry, Washington State University, Pullman, Washington, USA.
Kanako HayashiSchool of Molecular Biosciences, Center for Reproductive Biology, Washington State University, Pullman, Washington, USA.

Funding

Upgrade of confocal microscopy at the Oregon National Primate Research CenterP51OD011092 · OD · OREGON HEALTH & SCIENCE UNIVERSITY · PI Bonnie J. Nagel · 2012 to 2026
$203.9M
Complex inflammatory mechanisms and therapeutic targeting in endometriosisR01HD104619 · NICHD · WASHINGTON STATE UNIVERSITY · PI HAYASHI, KANAKO · 2021 to 2025
$2.4M
NICHD NIH HHS R01 HD104619NIH HHS P51 OD011092
6 · The paper itself

Abstract

This study investigated how chronic pelvic pain (CPP) develops using rhesus macaques with naturally occurring endometriosis and a multiple lesion induction mouse model (MIM), as repeated retrograde menstruation is considered an underlying mechanism of endometriosis pathogenesis. MIM increased lesion numbers and elevated hypersensitivity. Elevated persistent glial cell activation was observed across multiple brain regions or spinal cords in MIM and rhesus macaques. Elevated TRPV1, SP, and CGRP expressions in the dorsal root ganglia (DRG) were persistent in MIM. MIM induced the severe disappearance of TIM4hiMHCIIlo residential macrophages and an influx of increased pro-inflammatory TIM4loMHCIIhi macrophages in the peritoneal cavity. Cytokine levels were persistently elevated in MIM. Furthermore, dienogest (a synthetic progestin) and fingolimod (a selective immunosuppressor) reduced hyperalgesia and neuroinflammation. Our results indicate that recurrent retrograde menstruation can be a peripheral stimulus that induces nociceptive pain and creates a composite chronic inflammatory stimulus, leading to neuroinflammation and sensitization of the central nervous system. The circuits of neuroplasticity and stimulation of peripheral organs via a feedback loop of neuroinflammation may mediate widespread endometriosis-associated CPP. These findings in mice were further supported by results from the spontaneously developed advanced endometriosis in rhesus macaques via recurrent retrograde menstruation.

Indexed as

Central Nervous System SensitizationEndometriosisNeuroinflammatory DiseasesPelvic PainAnimalsDisease Models, AnimalFemaleGanglia, SpinalMacaca mulattaMacrophagesMiceInflammationMacrophagesReproductive biology

Identifiers

PMID41842953
PMCPMC13178660

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.