New findings by researchers at The Jackson Laboratory in Farmington show a deeper understanding of the excruciating pain women experience from endometriosis, a chronic inflammatory disease.
In patients with endometriosis, bits of the lining inside the uterus grow where they’re not supposed to — outside of it and on other organs. Jackson scientists studied tissue samples provided by Connecticut hospitals to document the signaling between neurons and immune cells that are clustered close to the endometriosis lesions.
“From that we're able to map how they interact, and now we can target those signaling mechanisms in order to create better treatment options,” said Caroline Haney, a postdoctoral associate at Jackson, who herself suffers from endometriosis.
“We needed to kind of understand the underlying biology a little more,” she said. “The best treatment options we have right now are often hormonal medications, and that doesn't work for a lot of people.”
Haney and her team created 3D models of sensory nerve tissue using the human stem cells to confirm their observations. They combined these models with cells taken from patient lesions. The findings, published in the journal Nature Communications, show interaction between the cells and nerves, and its relationship to the pain women experience.
"What we're really interested in is targeting the immune system,” Haney said. “Can we help the immune system calm down a little? Because it seems like the immune system is really creating this feedforward loop, where it's also really agitated and reacting.”
A Connecticut law that went into effect in 2024 puts the state’s resources to work to better understand endometriosis. The law established EndoRISE, the only state-funded program in the U.S. that carries endometriosis samples through its biorepository. The initiative also offers education, advocacy and awareness. The tissue samples for the Jackson study were provided through EndoRISE.
About 10% or 190 million women of reproductive age worldwide are affected by endometriosis, according to the World Health Organization.
“The diagnosis is typically delayed by approximately seven years as many women and healthcare providers are not familiar with the disease,” said Dr. Hugh Taylor, chair of obstetrics, gynecology and reproductive sciences at Yale School of Medicine.
Taylor said the first symptom is often painful menstrual periods, and the pain is often dismissed as normal.
“Women are often initially told that they are simply unable to handle normal cramps,” he said. “Sometimes endometriosis is not identified until one has disabling pain. This delay leads to years of the disease progressing leading to worsening pain and potentially infertility.”
But a better understanding of pain mechanisms in endometriosis may help doctors identify it sooner, Taylor said.
“Perhaps we can distinguish normal cramps from the more severe pain induced by endometriosis,” he said. “The findings in this paper may also lead to new treatment to block endometriosis pain.”
Dr. Kate Pascucci, an OBGYN in West Hartford, pointed out that societal attitudes have long normalized menstrual discomfort in ways that may delay recognition and treatment of significant pain. Doctors, she said, will need to move away from the assumption that severe menstrual pain is simply something women must endure.
“Pain relief and quality of life deserve to be central goals of endometriosis care, alongside fertility considerations when relevant to the patient,” she said.
Research into the chronic disease is important because it brings greater attention to endometriosis-associated pain and advances our understanding of its underlying mechanisms, Pascucci said.
"A better understanding of the neural pathways and other biological processes involved in pain may help identify new therapeutic targets and ultimately lead to more effective, individualized approaches to pain management,” she said.
