Endometriosis: The often overlooked cause of pain for millions of women

Endometriosis: The often overlooked cause of pain for millions of women

Pain-sensing nerves and immune cells work together to wreak havoc Endometriosis a painful condition that affects an estimated 190 million women and girls of childbearing age. However, a study in mice suggests a way to use this interaction to treat the disorder 1.

The research, published November 6 in Science Translational Medicine, reveals a crucial molecular pathway that not only... Pain sensations, which are caused by endometriosis, but also worsens the disease. Drugs that inhibit this pathway are already used to treat migraines - the study's findings suggest that these therapies could also be useful in treating endometriosis.

“This is a new perspective on how we might alter the pain pathways in endometriosis,” explains Louise Hull, a researcher who studies and treats endometriosis at the University of Adelaide in Australia.

Limited treatment options

Endometriosis occurs when cells similar to the tissue in the lining of the uterus grow outside the organ, occasionally causing pain, infertility, and heavy menstrual bleeding. Current treatment options are limited. Hormonal medications can relieve symptoms in some people, but not everyone can tolerate the side effects and they are not helpful for those trying to become pregnant. Nonsteroidal anti-inflammatory drugs are used to relieve pain, but long-term use can damage the liver and kidneys. The benefits of surgical treatments to remove endometrial plaque are often short-lived.

The disease is also is known to be under-researched says Michael Rogers, a cancer researcher at Boston Children's Hospital in Massachusetts and co-author of the study. “Compared to other diseases with similar prevalence and similar economic impact, research on endometriosis is underfunded by at least two – and probably three – orders of magnitude,” he points out.

Rogers was drawn to this field of research by a member of his church whose family was severely affected by endometriosis. Every month or two she would beg him: "She would say, 'Mike, you really need to start working on this disease.'"

Finally she convinced him. Rogers began pursuing research in this area and developed the animal models he needed to study the disease about nine years ago.

By then, researchers had already discovered that immune cells called macrophages likely contribute to endometriosis and that pain-sensing nerves are also involved 2. Rogers and his colleagues found that deactivating these nerves in mice with a condition similar to endometriosis not only reduced pain, as shown by the animals' behavior, but also reduced the size of the lesions containing endometrial cells. "This strongly suggested that the pain-sensing nerves not only sense pain, but also actively contribute to the growth of the lesions," says study co-author Victor Fattori, a pharmacologist at Boston Children's Hospital.

Interactions

The team decided to test whether a protein called CGRP, which helps communication between the nervous system and macrophages, might also play a role in endometriosis. Several drugs that block CGRP have already been approved by the U.S. Food and Drug Administration for other diseases, and researchers administered four of them to mice that are a model of endometriosis.

Here too, they observed a reduction in pain. Two of the drugs significantly reduced the size of the lesions, and it is possible that higher doses of the other two drugs would have had a similar effect, Rogers said.

Clinical trials are needed to determine whether the same approach could be effective in humans. Rogers is optimistic that such studies could begin soon: the drugs are already on the market and are considered relatively safe.

Still, it will be particularly important to demonstrate that they are safe for women who may want to become pregnant while taking the drug, Hull says.

If they are found to be safe and effective, CGRP-inhibiting drugs could fill a gap in treatment for people with endometriosis, says Erin Greaves, who studies the condition at the University of Warwick, UK, and works with Rogers. “New non-hormonal treatments for endometriosis are urgently needed.”

1. Fattori, V. et al. Sci. Transl. Med. 16, eadk8230 (2024).

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2. Garcia, J.M.G., et al. Reprod. Sci. 30, 1453-1461 (2023).

   
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