An idiographic approach to the neurobiological underpinnings of adolescent chronic pelvic pain

PROJECT SUMMARY Chronic pelvic pain (CPP) affects 15-20% of U.S. women of reproductive age and is linked to gynecological conditions, such as endometriosis and dysmenorrhea. Accumulating evidence suggests that altered pain processing in the brain (i.e., nociplastic pain, which predicts persistent comorbid pain disorders and treatment resistance) is an underlying cause in some cases. Despite the emergence of CPP during puberty, very little is known about how nociplastic pain manifests in adolescents, and neuroimaging studies are scarce. Furthermore, drastic changes to the CNS occur during puberty, with substantial heterogeneity that usually goes unexamined. Heterogeneity also characterizes the etiology, presentation, and neuroendocrinology of CPP in dysmenorrhea and endometriosis in adults. Thus, empirical research that centers on development and variability is necessary for meeting the unique needs of individuals who walk into clinics. The overarching goal of this proposal is to map the personalized neural variability underlying reproductive health-related CPP, informing important clinical outcomes by identifying risk factors and eventually improving early detection and intervention. The specific aims are to: 1) examine personalized neural networks involved in gynecological CPP in adult females; 2) identify individualized trajectories of dysmenorrhea pathogenesis, before and after menarche, and consequently, predict new pain onset in adolescence; and 3) conduct a longitudinal neuroimaging study to determine the heterogeneous neurobiological correlates of developing one or more Chronic Overlapping Pain Conditions from dysmenorrhea alone in adolescence. The main goals of the K99 portion are focused on providing the candidate innovative training in: a) pain phenotyping and neurobiology; b) idiographic methods, including developmental trajectories and personalized neural network analyses; and c) pubertal assessment. The K99 phase will take place at the University of Michigan (UM), under the mentorship of Dr. Adriene Beltz, a world-renowned expert in behavioral neuroendocrinology and developmental idiographic science. Drs. Chelsea Kaplan, Andrew Schrepf, and Daniel Clauw, internationally recognized experts in chronic pain mechanisms and neuroimaging, and Dr. Sawsan As-Sanie, an expert in clinical management of endometriosis and other CPP conditions, will also be mentors. The UM is an ideal training environment because of its extensive interdisciplinary resources, including the Department of Psychology, Chronic Pain and Fatigue Research Center, and the Department of Obstetrics and Gynecology. UM faculty mentors are leaders in their fields, have a history of successful collaboration, and are dedicated to data sharing and training. Upon completing the K99 portion, the candidate will be well-prepared to transition into an independent tenure-track faculty position studying neurobiological correlates and individualized mechanisms underlying the development of CPP conditions during adolescence. This work is crucial for women’s well-being, and highly novel in its focus on heterogeneity in the adolescent development of pain-related reproductive health disorders.