Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK.
MRC Centre for Reproductive Health, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
Reprod Fertil. 2021 Mar 23;2(1):47-57. doi: 10.1530/RAF-20-0072. eCollection 2021 Jan.
Endometriosis is a chronic neuroinflammatory pain condition affecting ~180 million women worldwide. Surgical removal or hormonal suppression of endometriosis lesions only relieves pain symptoms in some women and symptomatic relapse following treatment is common. Identifying factors that contribute to pain is key to developing new therapies. We collected peritoneal fluid samples and clinical data from a cohort of women receiving diagnostic laparoscopy for suspected endometriosis ( = 52). Peritoneal fluid immune cells were analysed by flow cytometry and data compared with pain scores determined using the pain domain of the Endometriosis Health Profile Questionnaire (EHP-30) in order to investigate the association between peritoneal immune cells and pain symptoms. Pain scores were not different between women with or without endometriosis, nor did they differ according to disease stage; consistent with a poor association between disease presentation and pain symptoms. However, linear regression and correlation analysis demonstrated that peritoneal macrophage abundance correlated with the severity of pelvic pain. CD14 peritoneal macrophages negatively correlated with pain scores whereas CD14 peritoneal macrophages were positively correlated, independent of diagnostic outcome at laparoscopy. Stratification by pain subtype, rather than endometriosis diagnosis, resulted in the most robust correlation between pain and macrophage adundance. Pain score strongly correlated with CD14 ( = 0.007) and CD14 ( = 0.008) macrophages in patients with non-menstrual pain and also in patients who reported dysmennorhea (CD14 = 0.021, CD14 = 0.019) or dysparunia (CD14 = 0.027, CD14 = 0.031). These results provide new insight into the association between peritoneal macrophages and pelvic pain which may aid the identification of future therapeutic targets.
Endometriosis is a common condition where cells similar to those that line the womb are found elsewhere in the body. It is associated with inflammation and pain in the pelvis and affects ~180 million women worldwide. Current treatments are not effective for all patients and we, therefore, need to understand what causes pain in order to develop new treatments. We investigated the types of immune cells present within the pelvis of women undergoing investigation for suspected endometriosis. Disease diagnosis and stage (I-IV) was recorded along with pain score determined by questionnaire. We characterised the immune cells present and compared them to disease stage and pain score. We found that pelvic pain was linked to the abundance of immune cells but, surprisingly, not to disease stage. These findings suggest that immune cells are closely associated with pain severity in endometriosis and may be good targets for future endometriosis treatments.
子宫内膜异位症是一种慢性神经炎症性疼痛疾病，影响全球约 1.8 亿名女性。对子宫内膜异位症病灶进行手术切除或激素抑制仅能缓解部分女性的疼痛症状，且治疗后症状复发较为常见。明确导致疼痛的因素是开发新疗法的关键。我们从接受疑似子宫内膜异位症诊断性腹腔镜检查的女性队列中收集了腹膜液样本和临床数据（ = 52）。通过流式细胞术分析腹膜液免疫细胞，并将数据与使用子宫内膜异位症健康状况调查问卷（EHP-30）的疼痛域确定的疼痛评分进行比较，以研究腹膜免疫细胞与疼痛症状之间的关联。患有子宫内膜异位症的女性和没有子宫内膜异位症的女性的疼痛评分没有差异，疾病阶段也没有差异；这与疾病表现与疼痛症状之间的关联较差一致。然而，线性回归和相关分析表明，腹膜巨噬细胞丰度与骨盆疼痛的严重程度相关。CD14 腹膜巨噬细胞与疼痛评分呈负相关，而 CD14 腹膜巨噬细胞与疼痛评分呈正相关，与腹腔镜检查时的诊断结果无关。按疼痛亚型而非子宫内膜异位症诊断进行分层，导致疼痛与巨噬细胞丰度之间的相关性最强。疼痛评分与非经期疼痛患者的 CD14（ = 0.007）和 CD14（ = 0.008）巨噬细胞以及报告痛经（CD14 = 0.021，CD14 = 0.019）或性交困难（CD14 = 0.027，CD14 = 0.031）的患者的 CD14 巨噬细胞呈强相关性。这些结果提供了腹膜巨噬细胞与骨盆疼痛之间关联的新见解，这可能有助于确定未来的治疗靶点。
子宫内膜异位症是一种常见的病症，即子宫内的细胞出现在身体的其他部位。它与骨盆中的炎症和疼痛有关，影响全球约 1.8 亿名女性。目前的治疗方法并非对所有患者都有效，因此我们需要了解引起疼痛的原因，以便开发新的治疗方法。我们研究了疑似子宫内膜异位症接受检查的女性骨盆内存在的免疫细胞类型。记录了疾病诊断和分期（I-IV）以及通过问卷确定的疼痛评分。我们对存在的免疫细胞进行了特征描述，并将其与疾病分期和疼痛评分进行了比较。我们发现，骨盆疼痛与免疫细胞的丰度有关，但令人惊讶的是，与疾病分期无关。这些发现表明，免疫细胞与子宫内膜异位症的疼痛严重程度密切相关，可能是未来子宫内膜异位症治疗的良好靶点。
