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

项目总结/摘要 子宫内膜异位症是育龄期青少年和妇女的常见疾病， 使人虚弱的骨盆疼痛、不孕症、生活质量下降和巨大的医疗保健费用。虽然一些患者 子宫内膜异位症患者将保持无症状或其症状将通过经验性治疗进行管理， 大约30%接受腹腔镜手术治疗子宫内膜异位症的女性会出现治疗抵抗性 慢性盆腔疼痛，这意味着虽然他们的盆腔炎病变已经切除，他们不会经历 疼痛治疗子宫内膜异位症患者慢性盆腔疼痛的一个潜在因素 患者是通过中枢敏感化引起的中枢神经系统的变化， 刺激。然而，很少有研究评估子宫内膜异位症妇女的中枢致敏作用， 没有人在青少年中进行评估。在子宫内膜异位症患者中， 病变与更大的糖尿病相关疼痛相关，这些疼痛水平可能会进一步放大， 腹膜腔内的促炎环境。在其他慢性疼痛状况中，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） 被认为与中枢致敏的发展有关。有限的研究评估了 子宫内膜异位症患者腹腔内神经营养因子与疼痛症状的关系 患者，并且没有研究前瞻性地评估了除了神经营养因子外的腹膜液水平。 炎症标志物与术后疼痛症状。我们的建议填补了这一科学空白， 研究腹腔液中β-NGF和BDNF水平是否与（1）共病疼痛相关 子宫内膜异位症患者中的病症（例如偏头痛，纤维肌痛），以及（2）区分 子宫内膜异位症患者谁将经历手术后的疼痛补救和那些谁不会，如果这 腹膜腔中的炎症环境改变了这种结合。此外，在探索 分析中，我们将评估腹膜腔中神经营养因子水平与 潜在的疼痛敏感性作为中枢敏感化的标志-迄今为止第一项研究，看看这些协会 在子宫内膜异位症患者中。总的来说，这些目标有可能促进我们对 子宫内膜异位症患者的慢性盆腔疼痛和中枢敏感性 重要的基础工作，进一步努力提供成功的个性化，精确的医疗， 最大限度地缓解疼痛。成功将降低医疗保健成本，提高长期健康和质量， 患有子宫内膜异位症的妇女和青少年的生活。

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.