Gut Microbiome Mechanisms of Multisensory Sensitivity in Primary Dysmenorrhea - PROJECT SUMMARY/ABSTRACT Menstrual pain is the most common gynecological condition, with recent prevalence rates estimated at 71.1% for adolescent girls and young women. Primary dysmenorrhea (PD; menstrual pain with no identified pathology) has a direct impact on functioning, particularly in adolescents, causing impairment in many life activities, including school, work, and social activities. Menstrual pain is also a known risk factor for chronic pain, but factors associated with this transition are still poorly understood. Research has mostly focused on the role of central sensitization of pain, although emerging evidence suggests PD is associated with sensitivity to non-painful sensory modalities (e.g., visual, auditory, tactile, and visceral) as well, known as multisensory sensitivity (MSS), suggesting systemic alterations in how sensory stimuli are processed. An extensive body of research has shown that alterations in the gut microbiome play a key, causal role in various chronic pain syndromes as well as contribute to heightened visceral and sensory perception and sensitivity. This suggests that gut microbiome composition contributes to MSS and the experience of pain, although it has not been examined in relation specifically in the context of PD. The proposed study will evaluate the relationship between gut microbiome composition, MSS, and the experience of pain in adolescent girls, ages 13-19, with moderate-to-severe primary dysmenorrhea. Measures of pain (menstrual pain severity, menstrual pain interference, and body pain), MSS (evaluated using a comprehensive battery of quantitative multisensory testing paradigms to determine pain, visual, auditory, tactile, and visceral sensitivities), and gut microbiome composition (obtained from a single stool sample) will be collected. In this study, we aim to characterize how gut microbiome composition is related to each pain and MSS in adolescents with primary dysmenorrhea. We hypothesize that gut microbiome composition (specifically diversity, functional profile, and lower abundancy of Lactobacillus) will be associated with higher pain and higher MSS. Findings from the study have the potential to advance our understanding of risk factors for chronic pain, as well as set the stage for future research to explore the trajectories of gut microbiome, pain, and MSS over time to ultimately develop new treatment approaches focused on reducing sensory sensitivity and interventions to alter gut microbiome composition.