2026-04-16 ワシントン州立大学（WSU）
＜関連情報＞
- https://news.wsu.edu/press-release/2026/04/16/why-endometriosis-causes-such-chronic-debilitating-pain/
- https://www.jci.org/articles/view/194136
子宮内膜症モデルにおいて、繰り返し起こる逆行性月経は神経炎症によって引き起こされる中枢性感作を増強する 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, and Kanako Hayashi
Journal of Clinical Investigation Published: March 17, 2026
Graphical Abstract
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 and/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 TIM4hi MHCIIlo residential macrophages and an influx of increased pro-inflammatory TIM4lo MHCIIhi 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.
