A new study from Washington State University published on Apr. 16 shows that repeated inflammation caused by endometriosis may rewire the brain and make pain last, even after lesions are removed. The research, led by Kanako Hayashi, professor in WSU's School of Molecular Biosciences, found that recurring cycles of inflammation can sensitize the nervous system and drive ongoing discomfort.
Endometriosis is a condition where tissue similar to the uterine lining grows outside the uterus. It affects more than 10 percent of women of reproductive age worldwide and often leads to severe pelvic pain and infertility. The study offers an explanation for why some patients continue to experience significant pain despite having few or no visible lesions.
Hayashi said, "We're showing that this is not just a local gynecological disease." She explained that there is often a mismatch between the extent of tissue growth and how much pain patients feel: "That mismatch tells us something more complex is happening. It's not just the lesions themselves. It's how the body and the nervous system respond over time."
To explore this issue, Hayashi's team developed a model simulating repeated menstrual cycles in mice, rather than inducing endometriosis-like conditions only once as most previous studies have done. Mice exposed to multiple cycles showed increased sensitivity and lasting changes in their nervous systems. Researchers observed higher levels of inflammation in both pelvic regions and nerve pathways leading up to neuroinflammation in the brain.
"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." Tissue samples from rhesus macaques with naturally occurring endometriosis supported these findings; no primate experiments were conducted at WSU.
The researchers found that once brain circuits responsible for processing pain become sensitized, they can keep generating pain signals even after lesion removal: "It becomes a feedback loop," Hayashi said. "The body is sending signals to the brain, and the brain is reinforcing those signals back to the body." Treatments targeting nervous system inflammation—rather than only removing lesions or suppressing hormones—may help reduce symptoms.
Looking ahead, Hayashi noted: "We now have a system where we can follow the entire process from the beginning... That gives us a powerful way to develop better treatments and, hopefully, detect the disease earlier."
