The pain of endometriosis is caused by an interaction between pain nerves and immune cells. This interaction also determines the size of the affected areas. That shows a study in mice and with tissue from eight patients which was published on Wednesday in the scientific journal Science translational medicine.
Endometriosis is a chronic inflammatory disease. Tissue that resembles the mucous membrane (the endometrium) that lines the uterus grows outside the uterus in this disease; for example around the ovaries or intestines. The mucosal tissue grows and shrinks during the menstrual cycle. The broken down mucous membrane and blood drain from the uterus every month. But this is not possible from other places in the abdominal cavity. This leads to chronic inflammation, adhesions and severe pain.
Surgical removal
The disease affects at least 1 in 10 women and also trans men, and is often unrecognized. Treatment consists of painkillers or hormones such as the contraceptive pill, which suppress the monthly cycle. Sometimes a surgeon can surgically remove the endometriosis spots.
The researchers looked at samples of endometriosis tissue from eight patients and studied lab mice into which they had injected uterine tissue into the abdominal cavity, a model for endometriosis. They discovered that endometriosis tissue contains the small protein CGRP. That molecule plays a role in pain. Pain-registering nerves, many of which are found in endometriosis tissue, also release it. It then binds to certain immune cells called macrophages, whose job is to clean up broken tissue. But because CGRP binds to those cells, these immune cells change in such a way that the endometriosis spots actually grow. The interaction therefore worsens the pain.
In the mice with endometriosis, the researchers tested four CGRP drugs approved in the US for the treatment of migraines (fremanezumab, galcanezumab, rimegepant and ubrogepant). All four reduced the mice’s sensitivity to pain, and in the animals given ubrogepant, the patches of endometriosis shrank.
A microscopic image of endometriosis tissue in which nerve fibers (green) influence the activity of immune cells (macrophages, red) that must clear damaged cells. Photo Victor Fattori and Michael Rodgers
Reimbursed under certain conditions
The first three migraine medications are also registered in Europe, and for chronic migraine, some CGRP inhibitors are reimbursed under certain conditions.
Good research, says Ellen Klinkert, gynecologist and head of the endometriosis center at the UMC Groningen. “We still know little about how endometriosis develops and what causes the pain, this study sheds light on that.”
Whether CGRP inhibitors will be a good option for patients with endometriosis remains to be seen. “Patients must use it for a long time to combat endometriosis; women suffer from it from the age of 12 to the age of 50. It must be carefully investigated whether such chronic use of these substances is safe. An advantage is that such a study can be set up more quickly with these existing resources than if it were new resources.”
Correction (November 7, 2024): An earlier version of this article stated that migraine patients only take CGRP inhibitors when an attack is approaching. That is not correct, they are also used chronically. It also stated that the resources are not reimbursed in the Netherlands. That is incorrect, for chronic migraine some CGRP inhibitors are reimbursed under certain conditions in the Netherlands. That has been adjusted above.
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‘Doctors keep saying: menstrual pain? Just get used to it’ Share Email the editor
Ah, endometriosis! The condition that turns the monthly gift of menstruation into an uninvited horror show. It’s the classic case of your body playing a game of “This isn’t what I ordered!” with all the worst side effects. Now, I don’t mean to make light of chronic pain—Lord knows that’s no laughing matter—but if we can’t laugh at the absurdity of it all, are we even living? Let’s dive into this fascinating article while we try to keep our gallows humor intact.
So, researchers have uncovered that the pain associated with endometriosis isn’t just some whimsical prank your body pulls. No, it’s a full-on scientific spectacle! It’s like a poorly cast play where pain nerves and immune cells dance a tango of torment. Honestly, you couldn’t make this up. These little drama queens, immune cells, take center stage and contribute to both the size of the affected areas and the lovely pain that comes along with it. And here we were thinking we only had to deal with emotional drama! The article cites a study in mice—because if there’s one thing you can count on, it’s that scientists are always going to test stuff on mice first. Sorry, little guys!
Surgical Removal
Let’s talk numbers—1 in 10 women and trans men get to enjoy the gift of endometriosis. Amazing, right? It’s like the worst club where the initiation rite involves chronic pain and emotional suffering. Treatment usually consists of a delightful cocktail of painkillers and hormones that do their best impressions of actual relief, but sometimes, if a miracle occurs, surgeons can swoop in like knights and remove those pesky endometriosis spots.
Researchers have found something interesting in endometriosis tissue from patients: a small protein called CGRP. Sounds fancy, doesn’t it? This molecule is basically the secret sauce that amplifies pain, binding to immune cells whose main job should be to clean up that broken tissue. But of course, just like a bad houseguest who keeps rearranging your furniture, CGRP makes these immune cells turn on the spots, which sounds like an extreme version of ‘make it bigger!’ Who knew our bodies were shopping for pain like teenagers on a weekend spree?
Now, here comes the fun part. In tests with mice—who are, let’s be honest, the real MVPs of medical research—the researchers tried out four CGRP drugs that are typically prescribed for migraines. Spoiler alert: these drugs did wonders for the little critters. All four of them had a positive impact, with one drug, ubrogepant, even shrinking those endometriosis patches. Not bad for a drug that was probably meant to keep your head from hurting, eh?
Reimbursed Under Certain Conditions
Unfortunately, as our gynecologist friend Ellen Klinkert points out, we still don’t know enough about how endometriosis develops. It’s like trying to figure out why your mate keeps texting their ex—they just don’t know when to let go! However, the potential for CGRP inhibitors offers a glimmer of hope, although it raises questions about long-term use. If women typically suffer from this condition from about the age of 12 to 50, can we really safely medicate them? Great! Now we’re in the delightful territory of ‘let’s weigh the risks and benefits’ while also trying to maintain our sanity.
And let’s not even get started on the corrections at the end of the article. Because if there’s one thing that’s always guaranteed in medical articles, it’s that someone will misinterpret something somewhere. A lesson to all of us: don’t trust everything you read on the internet—especially when it comes to your health!
But let’s wrap this up. Endometriosis is a multifaceted beast that affects millions with a combination of irritation, pain, and frustration. Research is ongoing, and while a humor-laden commentary can lighten the mood, awareness and empathy are key. At the end of the day, let’s hope this research will lead to a brighter future filled with actual solutions, not just more questions. And to all those out there facing the battle of endometriosis: you’re not alone, and science is—hopefully—on your side.
**Interview with Dr. Ellen Klinkert on the Recent Advances in Endometriosis Research**
**Host:** Welcome to our segment today! We have the pleasure of speaking with Dr. Ellen Klinkert, a gynecologist and head of the endometriosis center at UMC Groningen. She’s here to discuss a groundbreaking study on endometriosis and the role of CGRP neuropeptides in managing pain. Dr. Klinkert, thank you for joining us!
**Dr. Klinkert:** Thank you for having me! It’s a pleasure to discuss this important topic.
**Host:** Let’s dive right in. The recent study published in *Science Translational Medicine* highlights the interplay of pain nerves and immune cells in endometriosis. Can you explain why this finding is significant?
**Dr. Klinkert:** Absolutely! Understanding the interaction between pain nerves and immune cells is crucial as it directly impacts the experience of pain and the severity of endometriosis. The study shows that the small protein CGRP plays a pivotal role in amplifying pain and actually contributes to the growth of endometrial-like tissue outside the uterus. This is important because it sheds light on the biological mechanisms behind the chronic pain many patients experience.
**Host:** That’s fascinating! So, how does CGRP affect immune cells in the context of endometriosis?
**Dr. Klinkert:** CGRP binds to immune cells called macrophages, which are supposed to help clean up damaged tissue. However, instead of resolving inflammation, CGRP alters their function, leading to an increase in the size of the endometriosis lesions. This ultimately exacerbates the pain, creating a vicious cycle that’s difficult for patients to break free from.
**Host:** It sounds like a complex relationship! The study also tested CGRP drugs typically used for migraines. How effective were these treatments in the mouse models?
**Dr. Klinkert:** The results were promising. All four CGRP inhibitors tested reduced sensitivity to pain in the mice. Interestingly, one of the drugs, ubrogepant, not only alleviated pain but also caused a reduction in the size of endometriosis lesions. While these findings are exciting, we need to proceed with caution and further investigate the long-term safety and efficacy of these treatments in humans.
**Host:** Given that endometriosis impacts around 1 in 10 women and trans men, could CGRP inhibitors offer a new avenue for treatment?
**Dr. Klinkert:** Potentially, yes. If further studies confirm their safety and effectiveness, CGRP inhibitors could provide an additional option for patients who currently have limited relief from traditional pain management strategies. However, chronic use must be carefully examined, as endometriosis can persist over decades.
**Host:** That’s a crucial point. With many patients suffering in silence for years, what message would you like to convey to those affected by endometriosis?
**Dr. Klinkert:** It’s vital for patients to advocate for themselves and seek medical help if they experience symptoms of endometriosis. Education on the condition is key, as is ongoing research to uncover the best treatment methods. We’re improving our understanding, but there is still much to learn.
**Host:** Thank you so much, Dr. Klinkert, for sharing your insights on this important issue. We hope to see more advancements in the research for effective treatments for those suffering from endometriosis.
**Dr. Klinkert:** Thank you for having me! Let’s continue to raise awareness and support research in this area.
**Host:** Absolutely! Stay tuned for more discussions on health and wellness.
