Repeatedly occurring retrograde menstruation intensifies central sensitization driven by neuroinflammation in endometriosis models - PubMed
6 hours ago
- #endometriosis
- #chronic pain
- #neuroinflammation
- Chronic pelvic pain (CPP) development was studied using rhesus macaques with naturally occurring endometriosis and a multiple-lesion induction mouse model (MIM).
- Repeated retrograde menstruation is considered an underlying mechanism of endometriosis pathogenesis.
- MIM increased lesion numbers and elevated hypersensitivity, with persistent glial cell activation observed in multiple brain regions and spinal cords.
- Elevated TRPV1, SP, and CGRP expressions in the dorsal root ganglia (DRG) were persistent in MIM.
- MIM induced severe disappearance of TIM4hi MHCIIlo residential macrophages and an influx of pro-inflammatory TIM4lo MHCIIhi macrophages in the peritoneal cavity.
- Cytokine levels were persistently elevated in MIM.
- Dienogest (a synthetic progestin) and fingolimod (a selective immunosuppressor) reduced hyperalgesia and neuroinflammation.
- Recurrent retrograde menstruation can induce nociceptive pain and create a composite chronic inflammatory stimulus, leading to neuroinflammation and central nervous system sensitization.
- Neuroplasticity circuits and peripheral organ stimulation via neuroinflammation feedback loops may mediate widespread endometriosis-associated CPP.
- Findings in mice were supported by results from rhesus macaques with spontaneously developed advanced endometriosis via recurrent retrograde menstruation.