The early trajectory of menstrual pain intensity and the long-term impact of repeated exposure to menstrual pain on chronic pelvic pain (CPP) risk is unknown, despite the high prevalence of dysmenorrhea. Observational studies implicate both heightened menstrual pain and excess general bodily symptom awareness as strong risk factors for CPP emergence. Since current treatments for CPP have limited success, preventative strategies, targeting known risk factors, remain an urgent, unmet need. Menstrual pain, or dysmenorrhea, itself has a profound negative impact on quality of life for many women, and is refractory to treatment in 10-20% of adolescents. During pubertal development, neuroplasticity could permit repeated adverse sensory experiences from moderate-to-severe menstrual pain to establish multisensory hypersensitivity during adolescence, increasing the future risk for development of chronic pain. However, which patterns of menstrual pain create this vulnerability need to be determined, and how they effect such neural changes. Therefore, Aim 1 of this study will characterize the trajectory patterns of dysmenorrhea longitudinally over the two years post-menarche and determine the physiological and psychological factors defining these trajectories. To determine risk factors for persistent heightened dysmenorrhea, girls will be studied for two years of follow-up after menarche, using prospective menstrual symptom diaries along with careful cataloging of menstrual, psychosocial and developmental factors.
Aim 2 will then test whether the worst, persistent dysmenorrhea trajectory has the highest subsequent risk for multisensory hypersensitivity two years later, as a likely precursor to full blown CPP. Additionally, this aim will assess if change in risk of multisensory hypersensitivity following repeated menstrual pain is mediated by specific spinal or central mechanisms. Multisensory hypersensitivity will be measured by composite latent variable encompassing both self-reported symptom inventories and experimentally evoked responses to a standard battery of different sensory provocation tests. Specific mechanisms to be tested as mediators include prefrontal and primary sensory cortex activity, brainstem descending modulation of pain and peripheral pressure pain sensitivity using quantitative sensory testing and high-density EEG methods. The innovative experimental methods for measuring multisensory hypersensitivity (including non-invasive methods for measuring visceral sensitivity), with simultaneous kid-friendly electrophysiological measurements of brain activity, build on tools used by the combined research team, that is extensively engaged in uterine and pediatric pain assessment. Successful completion of this project, targeting the developmental timeline of chronic pelvic pain vulnerability, likely will define ideal windows for future preventative interventions and refine tools for evaluating visceral and multisensory sensitivity. Findings in this study will be uniquely valuable for understanding the transition from acute to chronic pain, a major public health priority.
The proposal addresses the NICHD mission to study the biology of reproductive processes and reduce suffering related to disorders of the uterus. A longitudinal study, using questionnaires and a battery of sensory tests, will characterize the initial course of menstrual pain (dysmenorrhea) during the early reproductive (menstrual) years to learn why some girls have continued strong pain with their periods. The results will also explore how having painful periods may contribute future risk for women to develop future excess pain sensitivity, which is strongly linked to eventually having a chronic pain disorder.
