Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Women's Centre, John Radcliffe Hospital, Oxford OX3 9DU, UK Department of Obstetrics and Gynaecology, University of Genoa, Genoa 16100, Italy
Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Women's Centre, John Radcliffe Hospital, Oxford OX3 9DU, UK.
Hum Reprod Update. 2014 Sep-Oct;20(5):717-36. doi: 10.1093/humupd/dmu021. Epub 2014 May 23.
Pain remains the cardinal symptom of endometriosis. However, to date, the underlying mechanisms are still only poorly understood. Increasing evidence points towards a close interaction between peripheral nerves, the peritoneal environment and the central nervous system in pain generation and processing. Recently, studies demonstrating nerve fibres and neurotrophic and angiogenic factors in endometriotic lesions and their vicinity have led to increased interest in peripheral changes in endometriosis-associated pain. This review focuses on the origin and function of these nerves and factors as well as possible peripheral mechanisms that may contribute to the generation and modulation of pain in women with endometriosis.
We conducted a systematic search using several databases (PubMed, MEDLINE, EMBASE and CINAHL) of publications from January 1977 to October 2013 to evaluate the possible roles of the peripheral nervous system in endometriosis pathophysiology and how it can contribute to endometriosis-associated pain.
Endometriotic lesions and peritoneal fluid from women with endometriosis had pronounced neuroangiogenic properties with increased expression of new nerve fibres, a shift in the distribution of sensory and autonomic fibres in some locations, and up-regulation of several neurotrophins. In women suffering from deep infiltrating endometriosis and bowel endometriosis, in which the anatomical distribution of lesions is generally more closely related to pelvic pain symptoms, endometriotic lesions and surrounding tissues present higher nerve fibre densities compared with peritoneal lesions and endometriomas. More data are needed to fully confirm a direct correlation between fibre density in these locations and the amount of perceived pain. A better correlation between the presence of nerve fibres and pain symptoms seems to exist for eutopic endometrium. However, this appears not to be exclusive to endometriosis. No correlation between elevated neurotrophin levels and pain severity appears to exist, suggesting the involvement of other mediators in the modulation of pain.
The increased expression of neurotrophic factors and nerve fibres in endometriotic lesions, eutopic endometrium and the peritoneum imply a role of such peripheral changes in the pathogenesis of endometriosis-associated pain. However, a clear link between these findings and pain in patients with endometriosis has so far not been demonstrated.
疼痛仍然是子宫内膜异位症的主要症状。然而，迄今为止，其潜在机制仍知之甚少。越来越多的证据表明，在外周神经、腹膜环境和中枢神经系统之间存在密切的相互作用，从而在疼痛的产生和处理中发挥作用。最近，一些研究表明，在子宫内膜异位症病灶及其附近存在神经纤维和神经营养及血管生成因子，这增加了人们对与子宫内膜异位症相关疼痛的外周变化的兴趣。本文重点关注这些神经和因子的来源和功能，以及可能有助于子宫内膜异位症患者产生和调节疼痛的外周机制。
我们使用多个数据库（PubMed、MEDLINE、EMBASE 和 CINAHL）系统地检索了 1977 年 1 月至 2013 年 10 月期间的文献，以评估外周神经系统在子宫内膜异位症病理生理学中的可能作用，以及它如何导致与子宫内膜异位症相关的疼痛。
患有子宫内膜异位症的女性的子宫内膜异位症病灶和腹腔液具有明显的神经血管生成特性，表现为新神经纤维的表达增加，一些部位感觉和自主神经纤维的分布发生变化，以及几种神经营养因子的上调。在患有深部浸润性子宫内膜异位症和肠子宫内膜异位症的女性中，病变的解剖分布通常与盆腔疼痛症状更为密切相关，与腹腔内病变和子宫内膜异位囊肿相比，子宫内膜异位症病灶和周围组织的神经纤维密度更高。需要更多的数据来充分证实这些部位的纤维密度与感知疼痛的程度之间存在直接相关性。对于在位子宫内膜，神经纤维的存在与疼痛症状之间似乎存在更好的相关性。然而，这种相关性似乎并不局限于子宫内膜异位症。神经生长因子水平升高与疼痛严重程度之间似乎没有相关性，这表明在疼痛的调节中涉及其他介质。
在子宫内膜异位症病灶、在位子宫内膜和腹膜中神经营养因子和神经纤维的表达增加，表明这些外周变化在子宫内膜异位症相关疼痛的发病机制中起作用。然而，迄今为止，尚未证明这些发现与子宫内膜异位症患者的疼痛之间存在明确的联系。
