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

项目摘要/摘要 子宫内膜异位症是育龄青少年和妇女的常见病，可导致 使人虚弱的骨盆疼痛、不孕不育、生活质量下降和巨大的医疗费用。虽然有些病人 子宫内膜异位症将保持无症状或其症状将通过经验性治疗得到控制， 接受腹腔镜子宫内膜异位症手术的女性中约有30%会出现治疗耐药 慢性盆腔疼痛，意味着虽然他们的子宫内膜异位病变已经切除，但他们不会经历 止痛药。导致子宫内膜异位症慢性盆腔疼痛的一个潜在因素 患者是通过中枢神经系统的变化引起的中枢敏感化，这种变化放大了疼痛 刺激物。然而，很少有研究评估患有子宫内膜异位症的妇女的中枢致敏作用。 没有人在青少年中对其进行评估。在子宫内膜异位症患者中，子宫内膜异位症的神经支配程度更高 病变与子宫内膜异位症相关的疼痛程度更大，这些疼痛水平可能会进一步放大 腹膜腔内的促炎环境。在其他慢性疼痛中，有两种神经 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 被认为参与了中枢敏感化的发展。有限的研究评估了 子宫内膜异位症患者腹膜腔内神经营养因子与疼痛症状的关系 患者，没有研究前瞻性地评估腹腔液中神经营养素的水平 具有术后疼痛症状的手术炎症标记物。我们的建议通过以下方式填补了这一科学空白 探讨腹腔液中β-神经生长因子和脑源性神经营养因子水平是否与共病疼痛有关 子宫内膜异位症患者的症状(例如偏头痛、纤维肌痛)，以及(2)区分 子宫内膜异位症患者将在手术后接受疼痛缓解，哪些患者不会，如果 相关性受到腹腔炎性环境的影响。此外，在探索性中 分析，我们将评估腹膜腔内神经营养素水平与 作为中枢敏感化标志的潜在疼痛敏感性--迄今为止首次研究这些关联 在子宫内膜异位症患者中。总而言之，这些目标有可能促进我们对 产卵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 在进一步努力提供成功的个性化、精准医疗方面的重要基础性工作 最大限度地缓解疼痛。成功将降低医疗成本，提高长期健康和医疗质量 青少年和患有子宫内膜异位症的妇女的生活。

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.