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

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.

摘要 子宫内膜异位症是一种使人衰弱的妇科疾病，表现为严重的盆腔疼痛，其特征是： 子宫外子宫样组织的生长影响了10%的育龄妇女， 估计全世界有2亿妇女和青少年。与没有子宫内膜异位症的女性相比， 子宫内膜异位症患者，尤其是患有子宫内膜异位症的青少年和年轻人， 慢性阿片类药物使用、依赖和过量。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，这是至关重要的，将对解决阿片类药物产生重大的积极影响。 健康危机。目前，子宫内膜异位症的主要治疗选择集中在激素抑制和/或 切除增生性病变，尽管对这些常规治疗的反应是可变的， 结果，许多子宫内膜异位症患者被持续的盆腔疼痛所困扰。新出现的证据表明 发生持续性盆腔疼痛的子宫内膜异位症患者发生了集中性疼痛，因此 外科手术切除肿瘤组织并不能完全改善他们的疼痛。由于许多女性被诊断为 子宫内膜异位症报告他们的症状开始于青春期，这种从急性到慢性疼痛的过渡是 可能发生在青春期和青年期。因此，研究青少年和年轻人， 子宫内膜异位症，谁是在他们的疾病轨迹的早期阶段，是至关重要的，以充分了解谁是在 患慢性疼痛的风险更高。然而，关于生物标志物和子宫内膜异位症的纵向变化的数据- 缺乏与青少年相关的疼痛，导致失去了早期干预的机会。总体 这一创新应用的目标是通过以下方式改善和优化子宫内膜异位症的疼痛管理： 鉴定患有慢性疼痛的青少年和年轻成人中慢性疼痛发展的血浆蛋白质生物标志物 子宫内膜异位症具体来说，我们建议对1999年至2000年诊断为子宫内膜异位症的病例进行纵向分析， 青少年的随访数据和配对血液样本收集10年，从青春期， 并应用最先进的7000-plex蛋白质组学测定来鉴定以下的血浆蛋白质生物标志物： 集中的慢性疼痛发展。此外，我们还将研究血浆蛋白质组学生物标志物的变化， 间隔10年（即青春期和成年期）抽取的配对血液样本， 资源将允许前瞻性调查的预测因素和生物学因素有关的过渡， 急性至慢性疼痛或慢性疼痛。这项研究的结果将产生重要的新数据 识别患有子宫内膜异位症的青少年和年轻女性，他们患慢性疼痛的风险更大 尽管接受了当前的护理标准，但导致了针对 年轻人口，以防止慢性疼痛，这将是一个关键的一步，以解决正在进行的 鸦片危机