Peripheral and central mechanisms of endometriosis pain

Abstract Endometriosis is a prevalent chronic painful condition in which an endometrial-like tissue lesion grows outside the uterus. The individual variability in endometriosis pain is large, and the factors contributing to it are unclear, but central and peripheral mechanisms have been proposed. Thus, this study aims to identify the mechanisms underlying endometriosis pain and the changes in pain after lesion removal surgery. We focus on central mechanisms of inhibitory pain modulation capabilities and systemic estrogen levels, as well as peripheral mechanisms involving estrogen receptor expression and local estrogen levels in the endometriosis lesion. We hypothesize that higher local and systemic estrogen levels and estrogen receptor expression in the lesion, and lower conditioned pain modulation (CPM) response will be related to greater endometriosis pain. In addition, we hypothesize that after the surgery, patients with higher estrogen receptor expression and higher local estrogen levels in the lesion (peripheral alterations) will have a greater reduction in endometriosis pain, while patients with lower CPM response and higher systemic estrogen levels (central alterations) will have a lower pain reduction. During the study, women with pelvic pain with and without endometriosis scheduled for an operative laparoscopic surgery for endometriosis diagnosis and/or treatment will complete a baseline study visit that includes a comprehensive characterization of their pain and endometriosis symptoms and psychophysical assessments of the CPM response. During the surgery, a blood sample for systemic estrogen level, a biopsy of the endometriosis lesion (if found), and a biopsy of healthy peritoneum will be collected and analyzed for local estrogen levels and estrogen receptor expression using quantitative PCR (qPCR), enzyme- linked immunoassay (ELISA) and western blot. After the surgery, patients will complete weekly surveys about their pain and symptoms for 3 months. Regression models will be used to identify the factors related to endometriosis pain and the change in pain after the surgery. A better understanding of endometriosis pain could improve the treatment of endometriosis pain. Future studies will identify new or repurpose existing pain treatments for endometriosis pain and develop a model that predicts which patients will have a significant pain reduction after the endometriosis removal surgery for a personalized medicine approach.