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

摘要 子宫内膜异位症是一种衰弱的妇科疾病，表现为严重的盆腔疼痛，其特征是 子宫外子宫内膜样组织的生长影响10%的育龄妇女或 据估计，全世界有2亿妇女和青少年。与未患子宫内膜异位症的女性相比， 患有子宫内膜异位症的人，特别是患有子宫内膜异位症的青少年和年轻人，患上子宫内膜异位症的风险增加。 慢性阿片类药物使用、依赖和过量。因此，优化子宫内膜异位症患者的疼痛管理， 尤其是从青春期开始，是至关重要的，并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 切除子宫内膜异位病变，尽管对这些常规治疗的反应是不同的，作为一种 结果，许多子宫内膜异位症患者都有持续性的盆腔疼痛。新出现的证据表明 患有持续性盆腔疼痛的子宫内膜异位症患者会出现集中性疼痛，因此 手术切除子宫内膜异位组织并不能完全改善他们的疼痛。因为许多被诊断为 子宫内膜异位症的症状始于青春期，这种从急性疼痛到慢性疼痛的过渡是 很可能发生在青春期和青春期。因此，研究青少年和年轻人 处于疾病轨迹早期阶段的子宫内膜异位症，对于充分了解谁处于 患慢性疼痛的风险更高。然而，关于生物标记物和子宫内膜异位症纵向变化的数据- 青少年缺乏相关的疼痛，导致失去了早期干预的机会。最重要的是 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 确定青少年和青壮年慢性疼痛发展的血浆蛋白生物标志物 子宫内膜异位症。具体地说，我们建议对#年诊断为子宫内膜异位症的病例进行纵向分析。 青春期与青春期相隔10年采集的随访数据和配对血样 并应用最先进的7000-plex蛋白质组学方法鉴定成人血浆蛋白生物标记物 集中、慢性疼痛的发展。此外，我们将检测血浆蛋白质组生物标记物的变化。 相隔10年(即青春期和成年期)提取的一对血液样本，这些独特的 资源将允许对与过渡相关的预测因素和生物因素进行前瞻性调查 急性到慢性疼痛或疼痛的慢性化。这项研究的结果将产生重要的新数据 确定患有子宫内膜异位症的青少年和年轻女性患慢性疼痛的风险更高 尽管接受了目前的护理标准，但导致了针对 年轻人口防止疼痛慢性化，这将是朝着解决正在进行的 阿片类药物危机。

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.