Kanako Hayashi
Image source: Washington State University
In a paper published in the Journal of Clinical Investigation, WSU scientist Kanako Hayashi and collaborators found that repeated cycles of inflammation can trigger lasting changes in the brain, amplifying and sustaining pain over time.
“We’re showing that this is not just a local gynecological disease,” said Hayashi, a professor in WSU’s School of Molecular Biosciences. “Once the system is sensitized, the brain keeps responding, even if the original lesions are gone.”
Endometriosis has long puzzled researchers because pain does not reliably match the extent of disease. Some patients with widespread lesions report little discomfort, while others with minimal tissue growth experience debilitating symptoms. “That mismatch tells us something more complex is happening,” Hayashi said. “It’s not just the lesions themselves. It’s how the body and the nervous system respond over time.”
To investigate, the research team designed a model that mimics repeated menstrual cycles. Most previous studies induced endometriosis-like conditions only once. Hayashi’s group instead introduced multiple cycles, simulating the repeated backflow of menstrual tissue called retrograde menstruation, thought to contribute to the disease.
Mice exposed to repeated cycles showed heightened sensitivity and lasting changes in the nervous system. Inflammation increased in the pelvic region, and signals traveled along nerve pathways to the spinal cord and brain, where researchers observed clear signs of neuroinflammation. “That repeated stimulation acts like turning up the volume again and again,” Hayashi said. “Eventually, the system becomes hypersensitive. Even small signals can feel very painful.”