A key cause for pelvic pain experienced by women with endometriosis has been discovered, potentially opening up new opportunities for pain relief for the condition.
Greaves' lab, now part of Warwick Medical School at the University of Warwick, along with employees at the University of Edinburgh, have discovered how our immune system cells play a role in stimulating growth and 39; activity of nerve cells in the condition, with greater sensitivity to pain in the pelvic region. The discovery was published today (July 11) in The FASEB Journal and was supported by funding from the Medical Research Council.
About 176 million women worldwide suffer from endometriosis, in which cells like the inner lining of the uterus (endometrium) grow outside it in the form of lesions, typically in the pelvic (peritoneal) cavity. It can cause significant pelvic pain and is associated with infertility for some women with this condition. Currently, treatment options are limited to surgical removal of the lesions or medical management to suppress the production of ovarian hormones. New non-hormonal treatments are desperately needed.
For this research the team focused on the role of macrophages, a type of white blood cell present in our immune system, in contributing to the pain caused by endometriosis. Macrophages adapt their functions according to local signals and are therefore modified by diseases. They are more attracted to the injuries of endometriosis and are also found in large quantities within the lesions themselves.
Using a cell culture of these diseased modified macrophages, scientists observed an increase in the production of insulin-like growth factor-1 (IGF-1). Applying this on nerve cells grown in culture, they discovered that this encouraged the nerves to grow and activated them, demonstrating that the production of IGF-1 by macrophages plays an important role in the generation of pain in endometriosis.
To further confirm their results, the researchers examined peritoneal fluid from women with endometriosis and found an increase in IGF-1 concentrations compared to those without the condition. Those women also reported having experienced higher levels of pain.
Previous studies have shown that macrophages can be involved in other types of chronic pain, but this is the first time it has been shown to be connected to endometriosis.
The lead author Dr Erin Greaves of Warwick Medical School stated: "The endometriosis is sometimes considered a" hidden disorder "due to the reluctance to discuss what can be transmitted as a" women's problem ". Hormonal solutions are based on suppression of 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 know the role of macrophages in endometriosis, we can distinguish them from healthy macrophages and target their treatment. Macrophages are so crucial to the function of our immune system and we need to learn more about their roles, so this research goes some way to defining how macrophages are different in endometriosis ".
It is known that macrophages change their function according to their local environment and therefore adopt a different gene expression in the presence of endometriosis lesions. While this acts to increase sensitivity to pain in that position, it can also serve as a potential marker for treatment.
The dott. Greaves added: "Endometriosis can affect women for life and is a very common condition. This discovery will help find ways to alleviate symptoms for women suffering from endometriosis. We hope that in the future we can learn exactly as the macrophages modified by the disease in the endometriosis promote the disease and how we can direct them towards the treatment of endometriosis ".
· "Insulin-like growth factor derived from macrophages-1 is a key neurotrophic and sensitizing factor of nerves in pain associated with endometriosis" published in The FASEB Journal, DOI: 10.1096 / fj.201900797R
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