Neurobiological Mechanisms of Stress in Youth with Chronic Widespread Pain

患有慢性广泛疼痛的青少年压力的神经生物学机制

• 批准号: 10686281
• 负责人: Sarah Mary Nelson
• 金额: $ 13.75万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10686281
• 关键词: Acute; Adult; Affect; Age; Anxiety; Area; Autonomic nervous system; Award; Blood Pressure; Body mass index; Boston; Brain; Cardiovascular system; Child; Childhood; Chronic stress; Clinical; Clinical Trials; Clinical Trials Design; Code; Communities; Complement; Data; Data Analytics; Development; Emotional Stress; Environment; Ethnic Origin; Evaluation; Exhibits; Exposure to; Foundations; Functional Magnetic Resonance Imaging; Future; Gender; Goals; Grant; Health Status; Heart Rate; Hippocampus; Home environment; Hospitals; Hydrocortisone; Impairment; Intervention; Investigation; Lipids; Longitudinal Studies; Maintenance; Measurement; Measures; Meditation; Mental Depression; Mentored Patient-Oriented Research Career Development Award; Mentorship; Mind-Body Intervention; Modeling; Nervous System; Neurobiology; Neurologic; Neurologic Dysfunctions; Neurosecretory Systems; Odds Ratio; Outcome; Pain; Pain Clinics; Pain management; Participant; Patients; Pediatric Hospitals; Physiological; Population; Public Health; Race; Recording of previous events; Reporting; Research; Research Activity; Research Personnel; Research Project Grants; Rest; Risk; Risk Factors; Role; Salivary; Schedule; Sleep; Stress; Stress Tests; Stressful Event; Structure; Sum; System; Techniques; Testing; Time; Training; Violence; Waist-Hip Ratio; Well Child Visits; Work; Youth; abuse neglect; adverse childhood events; allostatic load; career; central sensitization; chronic pain; chronic painful condition; chronic widespread pain; dehydroepiandrosterone; disability; experience; follow-up; functional disability; health care service utilization; hypothalamic-pituitary-adrenal axis; improved; longitudinal design; mindfulness-based stress reduction; neglect; neurobiological mechanism; neuroimaging; pain perception; pain reduction; pain-related disability; primary outcome; programs; psychologic; psychosocial; public health relevance; recruit; research study; response; secondary outcome; sex; stress reduction; treatment optimization; treatment services

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, violent/conflictual home environment, etc.) and a significant subset continue to experience physical and psychosocial impairment long-term. Certain mind-body interventions such as mindfulness-based stress reduction (MBSR) or meditation may be particularly appropriate for youth with CWP as they have been shown to modulate stress-induced maladaptation of the HPA-axis, autonomic nervous system, cardiovascular system, and brain structure (e.g., hippocampus). However, it is currently unknown if these targets are affected in youth with 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 youth with CWP. Mind-body interventions such as MBSR or meditation are an important and safe therapy option for both pain and stress reduction in youth with 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 pain-related impairment and responsiveness to mind-body interventions over time. 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 and improved compliance. 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. Chronic widespread pain was selected as a model condition because of its commonality within pediatric pain clinics and strong association with central sensitization, high stress, psychological impairment, and functional disability. The primary training objectives are to acquire expertise in neurobiological measurement and interpretation and to leverage current research activities in complement to this proposal that will lay the foundation for future 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 studies and training will provide the necessary data to inform the development of an R01 clinical trial designed to test the physiological mechanism(s) of response to MBSR, meditation, and other non-pharmacological techniques in youth with CWP.

项目总结/文摘

项目成果

Dissociative symptoms in youth with chronic pain: Worthy of future investigation?

慢性疼痛青少年的解离症状：值得未来研究吗？

• 发表时间: 2021
• 期刊: Pediatric pain letter
• 作者: Nelson,Sarah;Burns,Maureen;Kaczynski,Karen
• 通讯作者: Kaczynski,Karen

Hippocampal volume changes across developmental periods in female migraineurs.

• DOI: 10.1016/j.ynpai.2023.100137
• 发表时间: 2023-08
• 期刊: Neurobiology of pain (Cambridge, Mass.)
• 作者: Wilcox, Sophie L.;Nelson, Sarah;Ludwick, Allison;Youssef, Andrew M.;Lebel, Alyssa;Beccera, Lino;Burstein, Rami;Borsook, David
• 通讯作者: Borsook, David

Targeting the stress response in pediatric pain: current evidence for psychosocial intervention and avenues for future investigation.

• DOI: 10.1097/pr9.0000000000000953
• 发表时间: 2021-09
• 期刊: Pain reports
• 影响因子: 4.8
• 作者: Nelson S;Borsook D;Bosquet Enlow M
• 通讯作者: Bosquet Enlow M

Paediatric chronic pain as a catalyst for toxic stress.

• DOI: 10.1016/s2352-4642(22)00187-0
• 发表时间: 2022-10
• 期刊: LANCET CHILD & ADOLESCENT HEALTH
• 影响因子: 36.4
• 作者: Nelson, Sarah;Miller, Jillian Vinall;Timmers, Inge;Simons, Laura E.;Meldrum, Keith;Noel, Melanie
• 通讯作者: Noel, Melanie

Biomarkers of Allostatic Load as Correlates of Impairment in Youth with Chronic Pain: An Initial Investigation.

• DOI: 10.3390/children8080709
• 发表时间: 2021-08-18
• 期刊: Children (Basel, Switzerland)
• 作者: Nelson S;Bento S;Enlow MB
• 通讯作者: Enlow MB