Endometrial tissue that expands to invade the space surrounding nerve fibers may be an important contributing factor to the pain experienced by women with endometriosis, a study reports.
The study, “Perineural invasion in endometriotic lesions contributes to endometriosis-associated pain,” appeared in the Journal of Pain Research.
Chronic pain is a common symptom of endometriosis, with its most frequent manifestations being painful periods, painful sexual intercourse, and recurrent pelvic pain.
Although common, its cause is not fully understood. Factors associated with endometriosis-related pain include inflammation, hypersensitivity, oxidative stress, and anatomic distortion.
A complex network of cellular signals and tissue differentiation make up the underlying process of endometriosis. Studies have suggested that pain symptoms might be due to adhesive endometrium lesions infiltrating nerve fibers, or by these lesions releasing signals that promote the growth of new nerve cells.
Researchers in Guangzhou, China, explored possible connections between nerve invasion and deep infiltrating endometriosis, nerve cell response, and pain symptoms.
Their study enrolled 64 women with deep infiltrating endometriosis being treated at the First Affiliated Hospital of Sun Yat-sen University. Patients were asked to report their pain symptoms before undergoing surgical removal of the lesions.
A total of 24 women were found to have endometriosis infiltrating the uterosacral ligament (USL-DIE), six had endometriosis involving the rectovaginal septum (RVS-DIE), and 34 had both USL-DIE and RVS-DIE.
Analysis of the endometrial tissue removed by surgery showed that in 65.5% of USL-DIE cases, the lesion had invaded the space surrounding nerve cells in a process called perineural invasion (PNI). Such invasion was even more common in RVS-DIE samples, with 70% showing positive for perineural invasion.
Based on patient-reported symptoms, researchers found that perineural invasion was associated with significantly higher levels of painful periods and chronic pelvic pain. In patients with RVS-DIE, perineural invasion was also associated with higher levels of painful sexual intercourse.
Further analysis showed that the samples positive for PNI had significantly higher levels of the GAP-43 protein, a biomarker of newly formed nerve fibers. These samples were also found to have more blood vessels than usual.
GAP-43 levels in endometriosis tissue samples were evaluated next, and samples positive for perineural invasion were seen to have significantly higher protein levels (again, a marker for newly formed nerve fibers) than did samples without growth into surrounding nerves.
The team suggested these two events are associated, as the new nerve fibers were formed along with small blood vessels, “presenting a nerve-vessel network in the endometriotic lesion,” they wrote.
Although perineural invasion is a mechanism more frequently linked to malignant diseases, this study’s findings suggest that it may also be “an important and frequent phenomenon in deep infiltrating endometriosis.”
Perineural invasion has been found to be “closely related with endometriosis-associated pain,” the researchers wrote.
More studies are needed to better understand “how these interactions influence pain experience in women with endometriosis,” they concluded.
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