The news in brief
Yale researchers compared lesions from 19 women with or without pain: nearly 900 genes are expressed differently, and an inflammatory molecule, IL16, is linked to the intensity of pain. This is basic research on a small group: no test or treatment results from it yet.
What the study says
A team from the Yale School of Medicine, in the United States, put online on 10 September 2026, in the journal Molecular Human Reproduction, a study on a well-known puzzle for doctors: the extent of endometriosis lesions does not tell how much the disease hurts (Yale, 2026). Some patients have few lesions and disabling pain, others have extensive disease without any symptoms (Mamillapalli et al., 2026). Let us state at the outset that the full article is for subscribers only: we read its published abstract and the university's press release, not the full text.
The researchers analysed 27 biopsies of the peritoneum, the thin membrane lining the inside of the abdomen, taken from 19 patients: 9 with pain and 10 without pain (Mamillapalli et al., 2026). There are therefore more samples than patients, and the abstract does not say how they are distributed among them. In the patients without pain, the disease had been discovered by chance, during a laparoscopy performed for a problem unrelated to pelvic pain (Yale, 2026). RNA sequencing measures which genes are active in these tissues.
The figures to remember
First result: 890 genes are expressed differently in the lesions of patients in pain and in those of patients without symptoms (Mamillapalli et al., 2026). Among the clearest differences, the authors cite genes of inflammation signalling, including IL16, IL17RA and JAK3, genes of cell adhesion and genes linked to the modulation of nerves (Mamillapalli et al., 2026).
Next, an analysis by large sets of genes found 22 biological pathways that differed between the two groups, 7 of which concern immunity (Mamillapalli et al., 2026). A network analysis identified 11 clusters associated with the presence of pain, one of them very rich in immune and inflammatory functions (Mamillapalli et al., 2026).
Finally, the patients in pain were classified, according to clinical criteria, between mild pain and severe pain: six in the first case, three in the second (Yale, 2026). Among the molecules associated with pain, IL16 is the one the abstract identifies as also linked to its intensity (Mamillapalli et al., 2026). IL16 is a cytokine, a small protein that serves as a messenger for inflammation. According to the press release, protein assays in the biopsies point the same way as the genes, with more inflammatory molecules in the painful lesions (Yale, 2026); the abstract, for its part, does not give these figures.
How to read these results
The first limit is size. Nineteen patients in total, and only three in the severe pain group: with so few people, a correlation may be due to chance or to a few particular cases. These are clues, not a demonstration. Neither the abstract nor the press release mentions confirmation in a second group of patients.
The second limit is the nature of the link. The study shows an association: painful lesions have a particular molecular signature. It does not prove that IL16 causes the pain. The first author, Ramanaiah Mamillapalli, acknowledges this: other work will have to check whether this molecule is truly a driver of symptoms (Yale, 2026). His hypothesis is that IL16 would attract immune cells into the lesion, which would in turn produce other inflammation messengers, a cascade that would sustain the pain (Yale, 2026). This is a lead, not an established mechanism.
The third point concerns the comparison itself. The biopsies were fixed in formalin and stored in paraffin, a common technique in pathology (Mamillapalli et al., 2026). Above all, the patients without pain were operated on for other reasons: the two groups may therefore differ in ways other than pain, such as age or hormonal treatments. This is our reading; the abstract does not say how the authors accounted for these differences. Finally, the study was funded by the US National Institutes of Health, Yale University and the Endometriosis Foundation of America, a foundation dedicated to the disease (Yale, 2026).
What this changes for the reader
In the short term, nothing in care. No test and no treatment follows from this work. The team now wants to study whether drugs that block IL16 reduce endometriosis-related pain (Yale, 2026). This is a research prospect, not an available treatment.
The interest of this lead, according to the lead researcher Hugh Taylor, is that current pain treatments do not tackle its cause: identifying the source and blocking it would probably be more effective (Yale, 2026). This is a hope, not a result.
The immediate significance lies elsewhere. This study provides a biological basis for what many patients describe: pain is not measured by the size of the lesions. The national health insurance says so too, a single superficial lesion being able to hurt more than several (ameli.fr, 2026). Hugh Taylor adds that the pain of patients with few lesions is still often downplayed, and that no one should let these complaints be dismissed (Yale, 2026).
If your periods or sex are painful enough to disrupt your life, that is a reason to see someone, whatever the study of the moment. A doctor or a midwife will be able to assess the situation and refer you to the right professional.
What our main page adds
Our main page recalls a point that sheds light on this study: the intensity of pain says nothing about the extent of the lesions. Small lesions can hurt a great deal and large ones go unnoticed, which is among the reasons for diagnostic delay. It also takes stock of the research: no blood marker is validated, according to a Cochrane review of 141 studies, combinations of blood proteins remain to be confirmed, a saliva test has been usable in France since 2025 under a derogatory framework and the French National Authority for Health still judges it insufficiently demonstrated, and a lead using nanoparticles has only been tried in mice. See our page on endometriosis.
Going further
This news item is part of a broader topic, which our page Endometriosis: pain, fertility and intimate life covers in detail.
Read the page: Endometriosis: pain, fertility and intimate life