The role of neurotrophins in chronic pelvic pain and central sensitization among adolescents and women with endometriosis

神经营养素在患有子宫内膜异位症的青少年和女性慢性盆腔疼痛和中枢敏化中的作用

• 批准号: 10706494
• 负责人: Amy Lee Shafrir
• 金额: $ 26.11万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-19 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10706494
• 关键词: Adolescence; Adolescent; Adolescent and Young Adult; Adult; Affect; Biological Markers; Boston; Brain-Derived Neurotrophic Factor; Central Nervous System; Chronic; Communities; Data; Development; Diagnosis; Disease; Dysmenorrhea; Enrollment; Epidemiologic Methods; Etiology; Failure; Fibromyalgia; Genes; Genetic Polymorphism; Greater sac of peritoneum; Health; Health Care Costs; Heterogeneity; Hospitals; Infertility; Inflammatory; Laparoscopic Surgical Procedures; Lesion; Link; Longitudinal cohort study; Measurement; Measures; Migraine; Monitor; Myofascial Pain Syndromes; NGF-1beta; Nerve Growth Factors; Operative Surgical Procedures; Pain; Participant; Patients; Pelvic Pain; Peritoneal Fluid; Persistent pain; Postoperative Pain; Prediction of Response to Therapy; Quality of life; Research; Resistance; Role; Sampling; Selection for Treatments; Sensory; Stimulus; Symptoms; Testing; Woman; Women' s Health; Work; aged; algorithm development; central pain; central sensitization; chronic painful condition; chronic pelvic pain; cohort; comorbidity; endometriosis; experience; fibromyalgia pain; high reward; high risk; inflammatory marker; inflammatory milieu; innovation; multidisciplinary; nerve supply; neurotrophic factor; pain sensitivity; pain symptom; personalized medicine; precision medicine; prospective; remediation; reproductive; response; success; treatment response

Project Summary/Abstract Endometriosis is a common disease among reproductive-aged adolescents and women and can lead to debilitating pelvic pain, infertility, reduced quality of life and significant health care costs. While some patients with endometriosis will remain asymptomatic or their symptoms will be managed with empirical treatment, approximately 30% of women undergoing laparoscopic surgery for endometriosis will have treatment-resistant chronic pelvic pain, meaning that while their endometriotic lesions have been excised they will not experience pain remediation. One potential factor leading to the development of chronic pelvic pain among endometriosis patients is through central sensitization resulting from changes in the central nervous system that amplify painful stimuli. However, very few studies have assessed central sensitization among women with endometriosis and none have assessed it among adolescents. Among endometriosis patients, greater innervation of endometriotic lesions is associated with greater endometriosis-related pain and these pain levels may be further amplified by the pro-inflammatory environment within the peritoneal cavity. Among other chronic pain conditions, two nerve growth factors (neurotrophins) - β-nerve growth factor (β-NGF) and brain-derived neurotrophic factor (BDNF) are thought to be involved in the development of central sensitization. Limited research has assessed the relationship between neurotrophins within the peritoneal cavity and pain symptoms among endometriosis patients, and no studies have prospectively assessed the peritoneal fluid levels of neurotrophins in addition to inflammatory markers at surgery with post-surgery pain symptoms. Our proposal fills this scientific gap by investigating whether peritoneal fluid levels of β-NGF and BDNF are (1) associated with co-morbid pain conditions (e.g. migraine, fibromyalgia) among endometriosis patients, and (2) differentiate between endometriosis patients who will experience pain remediation after surgery and those who will not and if this association is modified by the inflammatory environment in the peritoneal cavity. Additionally, in exploratory analyses, we will assess the association between neurotrophin levels in the peritoneal cavity and measures of underlying pain sensitivity as markers of central sensitization – the first study to date to look at these associations among endometriosis patients. Collectively, these aims have the potential to advance our understanding of chronic pelvic pain and central sensitization among adolescents and women with endometriosis – laying important foundational work in furthering our efforts to provide successful personalized, precision medicine to maximize pain remediation. Success will reduce health care costs and increase long-term health and quality of life for adolescents and women with endometriosis.

项目概要/摘要 子宫内膜异位症是育龄青少年和妇女的常见疾病，可导致 一些患者会出现盆腔疼痛、不孕、生活质量下降和巨额医疗费用。 患有子宫内膜异位症的人将保持无症状，或者他们的症状将通过经验性治疗得到控制， 大约 30% 因子宫内膜异位症接受腹腔镜手术的女性会出现治疗耐药 慢性盆腔疼痛，这意味着虽然子宫内膜异位病变已被切除，但他们不会经历 疼痛治疗是导致子宫内膜异位症发生慢性盆腔疼痛的一个潜在因素。 患者通过中枢神经系统的变化引起的中枢敏化，加剧了疼痛 然而，很少有研究评估患有子宫内膜异位症和子宫内膜异位症的女性的中枢敏感性。 没有人对青少年子宫内膜异位症患者进行评估。 病变与子宫内膜异位症相关的更大疼痛有关，并且这些疼痛水平可能会进一步放大 在其他慢性疼痛状况中，腹膜腔内的促炎环境包括两种神经。 生长因子（神经营养因子）- β-神经生长因子（β-NGF）和脑源性神经营养因子（BDNF） 被认为参与中枢敏化的发展有限的研究已评估。 腹腔内神经营养因子与子宫内膜异位症疼痛症状的关系 患者，并且没有研究前瞻性地评估腹腔液中神经营养素的水平 我们的建议填补了这一科学空白。 研究腹腔液 β-NGF 和 BDNF 水平是否 (1) 与共病疼痛相关 子宫内膜异位症患者的病症（例如偏头痛、纤维肌痛），以及 (2) 区分 子宫内膜异位症患者在手术后会经历疼痛缓解，而不会经历疼痛缓解，如果 在探索过程中，这种关联还受到腹膜腔炎症环境的影响。 分析后，我们将评估腹膜腔中神经营养蛋白水平与测量值之间的关联 潜在的疼痛敏感性作为中枢敏化的标志——迄今为止第一项研究这些关联的研究 总的来说，这些目标有可能增进我们对子宫内膜异位症患者的理解。 患有子宫内膜异位症的青少年和妇女的慢性盆腔疼痛和中枢敏感化 – 产程 重要的基础工作，进一步推动我们为患者提供成功的个性化精准医疗 最大限度地缓解疼痛。成功将降低医疗保健成本并提高长期健康和质量。 患有子宫内膜异位症的青少年和妇女的生活。