Decoding Dysmenorrhea: Longitudinal Modeling of Pelvic Pain Phenotypes in Adolescents and Young Adults

PROJECT SUMMARY/ABSTRACT Menstrual pain, also known as dysmenorrhea, is the most common gynecological condition, with recent prevalence rates estimated at 71.1% for adolescent girls and young women. Whether due to the presence of an underlying tissue pathology, such as endometriosis (known as secondary dysmenorrhea; SD), or without any identified cause (known as primary dysmenorrhea; PD), individuals, particularly adolescents and young adults (AYAs), with menstrual pain experience significant disruptions to home, work, school, and social activities, resulting in negative impacts on educational and career attainment, mental health, social relationships, and overall life course potential. Little research has focused on identifying potential differences in the mechanisms of pain and clinical trajectory in those with SD compared to PD, although there is evidence that PD and SD share overlapping and distinct patterns in structural and functional connectivity of brain networks and impaired pain modulation, suggesting the possibility of both shared and unique neurobiological mechanisms underlying these conditions. The proposed study will evaluate the role of central pain processing in those with PD and SD by: (1) identifying a large sample of AYAs with and without dysmenorrhea, (2) investigating brain structure and function integrated with psychosocial and behavioral data, and (3) prospectively following the cohort for 2 years. Specifically, we will deeply phenotype 180 AYAs (age 14-25) with and without dysmenorrhea (60 with none to mild PD, 60 with moderate to severe PD, and 60 with surgically confirmed endometriosis-associated SD) using self-report [pain (including ecological momentary assessment (EMA) of pain during bleeding and non-bleeding days) and emotional functioning], behavioral [thermal and mechanical sensitivity, descending pain inhibition assessed using an offset analgesia (OA) paradigm], and brain [resting-state and task-based functional magnetic resonance imaging (fMRI) and structural MRI (sMRI)] measures to predict the trajectory of overall pain experience (pain severity, interference, and widespreadness) over 2 years. We hypothesize that pain experience is associated with impaired emotional, behavioral, and neural functioning, in both PD and SD, and that baseline indices of alterations in central pain processing results in increased overall pain severity, interference, and widespreadness over 2 years. Findings from the study will help identify the neurobiological and psychosocial underpinnings and developmental trajectories of dysmenorrhea, as well as unique pathways for dysmenorrhea phenotypes to determine (1) why dysmenorrhea persists (even after treatment), (2) the mechanisms of transition to adult diseases including chronic pelvic pain, and (3) potential biobehavioral targets for treatment and prevention of long-term morbidity.