The role of neurotrophins in chronic pelvic pain and central sensitization among adolescents and women with endometriosis

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Project Summary/Abstract Endometriosis is a common disease among reproductive-aged adolescents and women and can lead to debilitating pelvic pain, infertility, reduced quality of life and significant health care costs. While some patients with endometriosis will remain asymptomatic or their symptoms will be managed with empirical treatment, approximately 30% of women undergoing laparoscopic surgery for endometriosis will have treatment-resistant chronic pelvic pain, meaning that while their endometriotic lesions have been excised they will not experience pain remediation. One potential factor leading to the development of chronic pelvic pain among endometriosis patients is through central sensitization resulting from changes in the central nervous system that amplify painful stimuli. However, very few studies have assessed central sensitization among women with endometriosis and none have assessed it among adolescents. Among endometriosis patients, greater innervation of endometriotic lesions is associated with greater endometriosis-related pain and these pain levels may be further amplified by the pro-inflammatory environment within the peritoneal cavity. Among other chronic pain conditions, two nerve growth factors (neurotrophins) - β-nerve growth factor (β-NGF) and brain-derived neurotrophic factor (BDNF) are thought to be involved in the development of central sensitization. Limited research has assessed the relationship between neurotrophins within the peritoneal cavity and pain symptoms among endometriosis patients, and no studies have prospectively assessed the peritoneal fluid levels of neurotrophins in addition to inflammatory markers at surgery with post-surgery pain symptoms. Our proposal fills this scientific gap by investigating whether peritoneal fluid levels of β-NGF and BDNF are (1) associated with co-morbid pain conditions (e.g. migraine, fibromyalgia) among endometriosis patients, and (2) differentiate between endometriosis patients who will experience pain remediation after surgery and those who will not and if this association is modified by the inflammatory environment in the peritoneal cavity. Additionally, in exploratory analyses, we will assess the association between neurotrophin levels in the peritoneal cavity and measures of underlying pain sensitivity as markers of central sensitization – the first study to date to look at these associations among endometriosis patients. Collectively, these aims have the potential to advance our understanding of chronic pelvic pain and central sensitization among adolescents and women with endometriosis – laying important foundational work in furthering our efforts to provide successful personalized, precision medicine to maximize pain remediation. Success will reduce health care costs and increase long-term health and quality of life for adolescents and women with endometriosis.