Novel biomarkers and pathways of persistent endometriosis-associated pain across the life course

整个生命过程中持续性子宫内膜异位症相关疼痛的新生物标志物和途径

• 批准号: 10611090
• 负责人: Sawsan As-Sanie
• 金额: $ 82.85万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-23 至 2028-02-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10611090
• 关键词: Acute; Adolescence; Adolescent; Adult; Affect; Age; Back; Basic Science; Biological; Biological Markers; Biological Specimen Banks; Bladder; Blood; Blood specimen; Central Nervous System; Chronic; Clinical; Complex; Data; Development; Disease; Economics; Endometrial; Excision; Fatigue; Female; Functional Magnetic Resonance Imaging; Infertility; Inflammatory; Intervention; Intestines; Intractable Pain; Lesion; Life; Life Cycle Stages; Link; Longitudinal cohort; Magnetic Resonance Imaging; Measures; Michigan; Neurobiology; Neuroimmune; Operative Surgical Procedures; Pain; Pain Measurement; Participant; Pathway interactions; Patient Self-Report; Patients; Pelvic Pain; Peritoneal Fluid; Persistent pain; Phenotype; Plasma; Plasma Proteins; Prognostic Marker; Proteins; Proteomics; Protocols documentation; Quality of life; Questionnaires; Refractory; Reproducibility; Reproductive Health; Research; Resistance; Risk; Sampling; Selection for Treatments; Symptoms; Testing; Time; Tissues; Treatment outcome; Universities; Uterus; Woman; Women' s Health; aged; associated symptom; biomarker identification; chronic pelvic pain; clinical practice; cohort; common treatment; cost; endometriosis; experience; hormone therapy; inflammatory marker; innovation; link protein; neuroimaging; novel marker; reproductive; standard care; young woman

ABSTRACT. Endometriosis is a chronic inflammatory condition defined by the presence of endometrial-like tissue outside the uterus that often presents with pain and infertility, affecting approximately 10% of reproductive aged women. While some women respond well to hormonal therapy or surgical treatment, others do not and are plagued with continued or worsening pain. Many patients whose lives are substantially impacted by endometriosis associated pelvic pain (EAPP) experienced a transition from acute to persistent pain, often early in life, and subsequent worsening of symptoms. Once pain becomes persistent, it is often refractory to current treatments and may further evolve to include debilitating comorbid symptoms such as back, bladder and bowel pain, as well as widespread pain and fatigue. Identifying prognostic biomarkers associated with persistent and/or refractory EAPP would allow for strategic selection of treatments and interventions in vulnerable patients before pain becomes entrenched. Our overarching hypothesis is that neuroimmune/inflammatory markers can help identify women at risk for developing persistent and/or nociplastic pain. Specifically, we hypothesize that neuroimmune/inflammatory activity contributes to both the emergence and persistence of EAPP during adolescence, as well as the development of nociplastic pain in adults. Our preliminary analyses suggest that inflammatory and neuroimmune pathways are associated with more severe symptoms and may be implicated in the transition to persistent and/or refractory pain. In this proposal, we will leverage existing longitudinal questionnaire data and banked biospecimens (serial blood and peritoneal fluid) collected from females younger than 25 years participating in the Women’s Health Study: From Adolescence to Adulthood (A2A) to evaluate the emergence of EAPP. Further, following harmonized protocols we will collect blood samples, peritoneal fluid, and functional MRIs from a new cohort of adult women with established EAPP that began in adolescence who are undergoing both surgical and non-surgical therapies at the University of Michigan (UM) in order to evaluate markers of nociplastic EAPP. We will apply an innovative proteomics platform (basic science component) that has shown high reproducibility and can simultaneously measure >7,000 proteins. Detailed longitudinal assessment of endometriosis-associated symptoms (clinical/translational component), based on self-reported pain (both studies) and fMRI (UM cohort only), and biomarker quantification will be harmonized between the two cohorts to determine robust associations with persistent EAPP. By leveraging systemic and local biomarkers in combination with detailed pain assessment over time, this project is uniquely poised to identify biomarkers associated with persistent endometriosis-associated pain and emergence of nociplastic pain to advance our understanding of the underlying mechanisms that contribute to pelvic pain.

抽象的。子宫内膜异位症是一种由子宫内膜样的存在定义的慢性炎症疾病 子宫外通常表现出疼痛和不育的组织，影响了大约10％的生殖 老年妇女。虽然有些女性对荷尔蒙治疗或手术治疗的反应很好，但另一些妇女却没有，也没有 受到持续或恶化的疼痛困扰。许多生命受到重大影响的患者 子宫内膜异位症相关的骨盆疼痛（EAPP）经历了从急性到持续疼痛的过渡，通常很早就 在生活中，随后想知道症状。一旦疼痛持续，它通常对当前感到难治 治疗，可能进一步发展为包括衰弱的合并症症状，例如背部，膀胱和肠 疼痛以及宽度疼痛和疲劳。识别与持久性和/或相关的预后生物标志物 难治性EAPP将允许在弱势患者中进行战略选择治疗和干预措施 疼痛变得根深蒂固。我们的总体假设是神经免疫/炎症标记可以帮助 确定妇女患有持久性和/或nociplast疼痛的风险。具体来说，我们假设 神经免疫性/炎症活动有助于EAPP的出现和持久性 青少年，以及成人的鼻唇疼痛的发展。我们的初步分析表明 炎症性和神经免疫性途径与更严重的症状有关，可能与 过渡到持久和/或难治性疼痛。在此提案中，我们将利用现有的纵向 从女性收集的调查表数据和库存生物测量（连环血和腹膜液） 参加妇女健康研究超过25年：从青少年到成年（A2A）评估 Eapp的出现。此外，遵循协调方案，我们将收集血液样本，腹膜液和 来自新的成年妇女的职能MRI，始于青少年的EAPP 在密歇根大学（UM）接受手术和非手术疗法以评估 Nociplastic Eapp的标记。我们将应用一个创新的蛋白质组学平台（基础科学组件） 已经显示出很高的可重复性，并且可以轻松测量7,000种蛋白质。详细的纵向 基于自我报告的子宫内膜异位症相关符号（临床/翻译成分）的评估 疼痛（研究）和fMRI（仅COM队列），并且生物标志物定量将在两者之间进行协调 共同确定与持续的EAPP的牢固关联。通过利用系统性和本地生物标志物 随着时间的推移，该项目与详细的疼痛评估相结合，以识别生物标志物是独特的 与持续的子宫内膜异位症相关疼痛和肿瘤疼痛的出现有关，以促进我们的 了解导致骨盆疼痛的基本机制。