Neurobiological Mechanisms of Stress in Youth with Chronic Widespread Pain - Supplement

项目总结/文摘

Project Summary/Abstract Pediatric chronic widespread pain (CWP) is a serious public health problem resulting in high levels of healthcare utilization and disability. Youth with CWP also frequently report exposure to adverse childhood experiences (ACEs; abuse/neglect, etc.) and a significant subset continue to experience impairment long-term. Certain mind- body interventions such as mindfulness-based stress reduction (MBSR) may be particularly appropriate for pediatric CWP as they have been shown to modulate stress-induced maladaptation of the HPA-axis, autonomic nervous system, and brain structure (e.g., hippocampus). However, it is currently unknown if these targets are affected in pediatric CWP. Preliminary research indicates that allostatic load (AL), or “wear and tear” on the nervous system due to stress, may contribute to pain chronicity. Similarly, evidence suggests that the hippocampus, a brain structure that is among the most deleteriously affected by stress, plays a role in pain perception. However, no study to-date has examined AL and hippocampal functioning in relation to stress exposure in pediatric CWP. Mind-body interventions such as MBSR are an important and safe therapy option for both pain and stress reduction in pediatric CWP and may modulate the negative impact of ACEs, so there is a critical need to know if these mechanisms are engaged in this population. The proposed research project utilizes multifactorial physiological and neuroimaging measurement techniques to enhance our understanding of the potential role of these mechanisms in impairment and mind-body intervention response. The aims of this submission are to better characterize AL, assessed via a multifactorial composite, and hippocampal functioning via fMRI in pediatric CWP as specific targets for mind-body interventions that can lead to treatment optimization. The long-term goal of this K23 award is for the candidate to establish an independent research career aimed at carrying out mechanistically informed mind-body interventions. CWP was selected as a model condition because of its commonality within pediatric pain clinics and strong association with central sensitization, high stress, and functional disability. The primary training objectives are to acquire expertise in neurobiological measurement and interpretation and to leverage current research activities complementary to this proposal that will lay the foundation for mechanistically driven clinical trial grant submissions as an independent investigator. The candidate will accomplish this through: 1) mentorship in a clinical/research environment, 2) hands-on training in the neurobiological measurement of the physiological effects of stress, complemented by didactics in neuroendocrine and fMRI measurement, 3) mentorship and coursework in advanced data analytic techniques, 4) leveraging psychosocial practice activities and clinical trial involvement in conjunction with effort on the proposed award, and 5) execution of the proposed research plan and submission of an independent investigator award application. These activities will provide the necessary data to inform the development of an R01 clinical trial designed to test the physiological mechanism(s) of mind-body intervention response in youth with CWP.