Identifying plasma proteomic profiles of chronic pain development in endometriosis from adolescence to adulthood

鉴定从青春期到成年期子宫内膜异位症慢性疼痛发展的血浆蛋白质组谱

• 批准号: 10685659
• 负责人: Naoko Sasamoto
• 金额: $ 131.23万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-19 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10685659
• 关键词: Adolescence; Adolescent; Adolescent and Young Adult; Adult; Biological Assay; Biological Factors; Biological Markers; Blood specimen; Chronic; Data; Dependence; Development; Diagnosis; Disease; Early Intervention; Endometrial; Excision; Female Genital Diseases; Goals; Growth; Health; Hormonal; Intervention; Investigation; Lesion; Opioid; Overdose; Pain; Pain management; Patients; Pelvic Pain; Plasma; Plasma Proteins; Population; Predictive Factor; Proteomics; Reporting; Resources; Risk; Symptoms; Tissues; Uterus; Woman; aged; central pain; chronic pain; conventional therapy; endometriosis; follow-up; high risk; improved; innovation; longitudinal analysis; novel; novel strategies; opioid epidemic; opioid use; opioid user; pain chronification; pandemic disease; prevent; prospective; protein biomarkers; reproductive; response; standard of care; young adult; young woman; Adolescence; Adolescent; Adolescent and Young Adult; Adult; Biological Assay; Biological Factors; Biological Markers; Blood specimen; Chronic; Data; Dependence; Development; Diagnosis; Disease; Early Intervention; Endometrial; Excision; Female Genital Diseases; Goals; Growth; Health; Hormonal; Intervention; Investigation; Lesion; Opioid; Overdose; Pain; Pain management; Patients; Pelvic Pain; Plasma; Plasma Proteins; Population; Predictive Factor; Proteomics; Reporting; Resources; Risk; Symptoms; Tissues; Uterus; Woman; aged; central pain; chronic pain; conventional therapy; endometriosis; follow-up; high risk; improved; innovation; longitudinal analysis; novel; novel strategies; opioid epidemic; opioid use; opioid user; pain chronification; pandemic disease; prevent; prospective; protein biomarkers; reproductive; response; standard of care; young adult; young woman

ABSTRACT Endometriosis is a debilitating gynecologic disease presenting with severe pelvic pain and is characterized by the growth of endometrial-like tissue outside of the uterus impacting 10% of reproductive aged women or an estimated 200 million women and adolescents worldwide. Compared to women without endometriosis, women with endometriosis, especially adolescents and young adults with endometriosis, are at an increased risk of chronic opioid use, dependence, and overdose. Therefore, optimal pain management in endometriosis patients, especially starting in adolescence, is critical and will have significant positive impact on resolving the opioid health crisis. Currently, primary treatment options for endometriosis focus on hormonal suppression and/or excision of the endometriotic lesions, although response to these conventional treatments is variable and as a result, many of those with endometriosis are plagued with persistent pelvic pain. Emerging evidence suggests that endometriosis patients who develop persistent pelvic pain have developed centralized pain, and therefore surgical removal of endometriotic tissue does not fully improve their pain. Since many women with diagnosed endometriosis report their symptoms started during adolescence, this transition from acute to chronic pain is likely happening during adolescence and young adulthood. Thus, studying adolescents and young adults with endometriosis, who are in the early stages of their disease trajectory, is critical to fully understanding who is at higher risk of developing chronic pain. However, data on longitudinal changes in biomarkers and endometriosis- associated pain in adolescents is lacking, resulting in lost opportunity for early interventions. The overarching goal of this innovative application is to improve and optimize pain management for endometriosis through identifying plasma protein biomarkers of chronic pain development in adolescents and young adults with endometriosis. Specifically, we propose to conduct a longitudinal analysis of endometriosis cases diagnosed in adolescence with follow-up data and paired blood samples collected 10 years apart from adolescence to adulthood and apply a state of the art 7000-plex proteomics assay to identify plasma protein biomarkers of centralized, chronic pain development. In addition, we will examine change in plasma proteomic biomarkers in paired blood samples drawn 10 years apart (i.e. at adolescence and adulthood), and together these unique resources will allow prospective investigation of predictors and biological factors related to transitioning from acute to chronic pain or chronification of pain. Results from this study will generate important novel data identifying adolescents and young women with endometriosis who are at greater risk of developing chronic pain despite receiving current standard of care, leading to development of novel pain interventions targeted to a younger population to prevent chronification of pain, which will be a critical step forward to resolving the ongoing opioid crisis.

抽象的 子宫内膜异位症是一种使人衰弱的妇科疾病，表现出严重的骨盆疼痛，其特征是 子宫外子宫样组织的生长在子宫外影​​响10％的生殖老年妇女或 全球估计有2亿妇女和青少年。与没有子宫内膜异位的女性相比 子宫内膜异位症，尤其是青少年和子宫内膜异位症的年轻人的风险增加 慢性阿片类药物的使用，依赖性和过量。因此，子宫内膜异位症患者的最佳疼痛管理， 特别是从青春期开始，至关重要，将对解决阿片类药物产生重大积极影响 健康危机。目前，子宫内膜异位症的主要治疗方案集中于激素抑制和/或 切除子宫内膜损伤，尽管对这些常规治疗的反应是可变的，并且是 结果，许多子宫内膜异位症的人都会持续存在骨盆疼痛。新兴证据表明 那些出现持续性盆腔疼痛的子宫内膜异位症患者已经产生了集中疼痛，因此 手术清除子宫内膜组织不会完全改善其疼痛。由于许多有诊断的妇女 子宫内膜异位症报告它们的症状始于青春期，这种从急性到慢性疼痛的过渡是 可能在青春期和成年期间发生。因此，研究青少年和年轻人 子宫内膜异位症正处于疾病轨迹的早期阶段，对于完全了解谁在 患慢性疼痛的风险更高。但是，关于生物标志物和子宫内膜异位症的纵向变化的数据 缺乏青少年的相关疼痛，从而导致早期干预的机会失去了机会。总体 这种创新应用的目标是改善和优化通过 鉴定青少年和年轻人的血浆蛋白生物标志物 子宫内膜异位症。具体而言，我们建议对诊断为诊断的子宫内膜异位症病例进行纵向分析 青春期，随访数据和配对的血液样本从青春期到 成年并应用最新的7000-plex蛋白质组学测定法以鉴定血浆蛋白生物标志物 集中的慢性疼痛发展。此外，我们将检查血浆蛋白质组学生物标志物的变化 配对的血液样本相距10年（即在青春期和成年时），并将这些独特 资源将允许对与过渡有关的预测因素和生物因素的预期调查 急性到慢性疼痛或疼痛的年代表。这项研究的结果将产生重要的新数据 确定患有慢性疼痛的风险更大的子宫内膜异位症的青少年和年轻女性 尽管接受了当前的护理标准，导致针对A的新型疼痛干预措施的发展 较年轻的人群以防止疼痛的逐渐化，这将是解决持续的迈出的重要一步 阿片类药物危机。