ABSTRACT
Endometriosis is a debilitating gynecologic disease presenting with severe pelvic pain and is characterized by
the growth of endometrial-like tissue outside of the uterus impacting 10% of reproductive aged women or an
estimated 200 million women and adolescents worldwide. Compared to women without endometriosis, women
with endometriosis, especially adolescents and young adults with endometriosis, are at an increased risk of
chronic opioid use, dependence, and overdose. Therefore, optimal pain management in endometriosis patients,
especially starting in adolescence, is critical and will have significant positive impact on resolving the opioid
health crisis. Currently, primary treatment options for endometriosis focus on hormonal suppression and/or
excision of the endometriotic lesions, although response to these conventional treatments is variable and as a
result, many of those with endometriosis are plagued with persistent pelvic pain. Emerging evidence suggests
that endometriosis patients who develop persistent pelvic pain have developed centralized pain, and therefore
surgical removal of endometriotic tissue does not fully improve their pain. Since many women with diagnosed
endometriosis report their symptoms started during adolescence, this transition from acute to chronic pain is
likely happening during adolescence and young adulthood. Thus, studying adolescents and young adults with
endometriosis, who are in the early stages of their disease trajectory, is critical to fully understanding who is at
higher risk of developing chronic pain. However, data on longitudinal changes in biomarkers and endometriosis-
associated pain in adolescents is lacking, resulting in lost opportunity for early interventions. The overarching
goal of this innovative application is to improve and optimize pain management for endometriosis through
identifying plasma protein biomarkers of chronic pain development in adolescents and young adults with
endometriosis. Specifically, we propose to conduct a longitudinal analysis of endometriosis cases diagnosed in
adolescence with follow-up data and paired blood samples collected 10 years apart from adolescence to
adulthood and apply a state of the art 7000-plex proteomics assay to identify plasma protein biomarkers of
centralized, chronic pain development. In addition, we will examine change in plasma proteomic biomarkers in
paired blood samples drawn 10 years apart (i.e. at adolescence and adulthood), and together these unique
resources will allow prospective investigation of predictors and biological factors related to transitioning from
acute to chronic pain or chronification of pain. Results from this study will generate important novel data
identifying adolescents and young women with endometriosis who are at greater risk of developing chronic pain
despite receiving current standard of care, leading to development of novel pain interventions targeted to a
younger population to prevent chronification of pain, which will be a critical step forward to resolving the ongoing
opioid crisis.