Department of Gynecology Charité with Center of Oncological Surgery, Endometriosis Research Center Charité, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany.
Int J Mol Sci. 2023 Jan 13;24(2):1633. doi: 10.3390/ijms24021633.
Endometriosis (EM), defined as the presence of endometrial-like tissue with surrounding smooth muscle cells outside the uterus, is a disregarded gynecological disease reported to affect 6-10% of women of reproductive age, with 30-50% of them suffering from chronic pelvic pain and infertility. Since the exact pathogenic mechanisms of EM are still unclear, no curative therapy is available. As pain is an important factor in EM, optimal analgesia should be sought, which to date has been treated primarily with non-steroidal anti-inflammatory drugs (NSAIDs), metamizole or, in extreme cases, opioids. Here, we review the pain therapy options, the mechanisms of pain development in EM, the endogenous opioid system and pain, as well as the opioid receptors and EM-associated pain. We also explore the drug abuse and addiction to opioids and the possible use of NOP receptors in terms of analgesia and improved tolerability as a target for EM-associated pain treatment. Emerging evidence has shown a promising functional profile of bifunctional NOP/MOP partial agonists as safe and nonaddictive analgesics. However, until now, the role of NOP receptors in EM has not been investigated. This review offers a thought which still needs further investigation but may provide potential options for relieving EM-associated pain.
子宫内膜异位症（EM）定义为子宫外存在具有周围平滑肌细胞的子宫内膜样组织，是一种被忽视的妇科疾病，据报道影响 6-10%的育龄妇女，其中 30-50%患有慢性盆腔痛和不孕。由于 EM 的确切发病机制仍不清楚，因此尚无有效的治疗方法。由于疼痛是 EM 的一个重要因素，因此应寻求最佳的镇痛治疗，迄今为止，主要采用非甾体抗炎药（NSAIDs）、甲灭酸或在极端情况下使用阿片类药物进行治疗。在这里，我们回顾了疼痛治疗的选择、EM 中疼痛发展的机制、内源性阿片系统和疼痛以及阿片受体和与 EM 相关的疼痛。我们还探讨了阿片类药物滥用和成瘾以及 NOP 受体在镇痛和改善耐受性方面的可能用途，作为治疗与 EM 相关疼痛的靶点。新出现的证据表明双功能 NOP/MOP 部分激动剂具有有希望的功能特征，可作为安全且无成瘾性的镇痛药。然而，到目前为止，NOP 受体在 EM 中的作用尚未得到研究。这篇综述提出了一个仍需要进一步研究的观点，但可能为缓解 EM 相关疼痛提供了潜在的选择。
