Central sensitization and somatic activating KRAS mutations in endometriosis-associated pain

Endometriosis is the presence of endometrial-like tissue growing abnormally outside the uterus and affects 10% of women and an unknown number of gender diverse people. There are 3 anatomical types of endometriosis: superficial peritoneal (SUP), ovarian endometrioma (OMA), and deep infiltrating endometriosis (DIE). Pelvic pain is a cardinal symptom in endometriosis. The etiology of pelvic pain in endometriosis is multifactorial, meaning that multiple factors may play a role in this pain, such as central nervous system sensitization and peripheral factors (e.g., somatic mutations in endometriosis lesions). Central nervous system amplification of pain pathways (central sensitization) has been found in people with endometriosis and pelvic pain, which manifests as non-gynecologic pain contributors (central sensitivity syndromes (CSS)). In Chapter 2, I hypothesized that the Central Sensitization Inventory (CSI) could be used to identify centrally sensitized people in an endometriosis population and predict surgical outcomes. My results indicated that a CSI cut-off of 40 or higher could identify a person with 3 or more CSS with good sensitivity and specificity. Additionally, recent findings showed that 25% of DIE (without concurrent cancer) harbour somatic activating mutations of the KRAS oncogene in endometriosis epithelial cells. In Chapter 3, I explored the prevalence of somatic activating KRAS codon 12 mutations in endometriosis lesions and their association with clinical variables (e.g., pain scores). My results indicated that OMA samples had the highest KRAS mutation prevalence compared to the other anatomical types. Additionally, KRAS mutations were associated with more severe anatomic disease (i.e., higher stage and more invasive endometriosis). In Chapter 4, I addressed the gap between evidence and practice by translating research findings in a one-day workshop and an accessible video format to patients with endometriosis and their loved ones. My results indicated that a one-day workshop on sexual pain and endometriosis showed promise at improving confidence in self-managing sexual pain and improving knowledge on endometriosis, as well as intent for behavioral changes. Overall, my dissertation work may inform a future clinical decision aid to identify the primary factors contributing to endometriosis pain and suggest specific therapies to treat those factors and reduce unnecessary procedures.