Immune cells are behind endometriosis pain

Scientists have uncovered a key cause for the pelvic pain associated with endometriosis.

The discovery may open new opportunities for pain relief for the condition.

The new study shows how cells in our immune system play a role in stimulating the growth and activity of nerve cells in the condition, which leads to increased sensitivity to pain in the pelvic region.

Around 176 million women worldwide suffer from endometriosis, in which cells like the internal lining of the uterus (endometrium) grow outside of it in the form of lesions, typically in the pelvic (peritoneal) cavity.

The condition can cause significant pelvic pain and is associated with infertility for some women. Currently, treatment options are limited to surgical removal of lesions or medical management to suppress ovarian hormone production. New non-hormonal treatments are desperately needed.

Endometriosis and immune cells

For the new study, researchers focused on the role of macrophages, a type of white blood cell found in our immune system. Macrophages adapt their functions according to local signals, so disease can modify them. They are drawn to endometriosis lesions and are also found in high numbers inside the lesions themselves.

Using a cell culture of these disease-modified macrophages, the scientists observed increased production of the insulin-like growth factor-1 (IGF-1). Applying this onto nerve cells grown in culture, they found that this encouraged the nerves to grow and also activated them, which shows that production of IGF-1 by macrophages plays an important role in generating pain in endometriosis.

To further confirm their results, the researchers examined peritoneal fluid from women with endometriosis and found increased concentrations of IGF-1 compared to those without the condition. Those women also self-reported experiencing greater levels of pain.

Previous studies have shown that macrophages can be involved in other types of chronic pain, but this is the first time researchers have shown their link to endometriosis.

‘Hidden disorder’

“Endometriosis is sometimes considered a ‘hidden disorder’ because of a reluctance to discuss what can be passed off as ‘women’s problems,'” says lead author Erin Greaves from Warwick Medical School at the University of Warwick.

“Hormonal solutions rely on suppressing ovarian function but are not ideal as they can cause unwanted side effects, and prevent the user from becoming pregnant. We are trying to find non-hormonal solutions.

“If we can learn about the role of macrophages in endometriosis then we can distinguish them from healthy macrophages and target treatment to them. Macrophages are so crucial to our immune system tissue function and we need to know more about their roles, so this research goes some way in defining how macrophages are different in endometriosis,” she says.

Macrophages are known to change their function based on their local environment and so adopt a different gene expression in the presence of endometriosis lesions. While this acts to increase the sensitivity to pain in that location, it may also act as a potential marker to target for treatment.

“Endometriosis can affect women throughout their lives and is a very common condition,” Greaves says. “This discovery will go some way towards finding ways to relieve symptoms for women who suffer from endometriosis. We hope that in the future we can learn exactly how disease-modified macrophages in endometriosis promote disease and how we can target them in order to treat endometriosis.”

The research appears in the FASEB Journal.

Additional researchers are from the University of Warwick and the University of Edinburgh.

Source: University of Warwick

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