Polypropylene mesh is frequently used in urogynecology procedures; however, pain and mesh exposure into the vagina occur in ~10% of cases. Mesh-induced pain, which occurs with or without exposure, persists after removal in 50% of cases. Chronic pain history predicts poor response to mesh removal but only a fraction have this diagnosis. We hypothesize that mesh induced pain is correlated with fibrosis and failure to improve with a heightened inflammatory and fibrotic host response. Women undergoing mesh removal were offered participation in a mesh biorepository. Standardized questionnaires including visual analog scale (VAS) pelvic pain scores were completed at enrollment and 6 months after removal. Responders were considered those with ≥13 mm VAS improvement. 30 mesh-tissue explants were randomly selected for analysis. Samples were labeled for CD8, CD4 (T_h) and FoxP3 (T_regs). Peri-fiber collagen deposition (fibrosis) was measured using a customized semi-quantitative assay. Concentrations of TGF-b1, bFGF, MCP-1, PDGF-BB, and IGFBP-1 in tissue were determined by immunoassay and compared to vaginal control biopsies with pathway analysis. VAS pain scores were correlated with degree of histologic fibrosis. Responders had more T_regs (7.8 vs 0.3 per mm², p = 0.036) and patients were 1.6 times as likely to be a responder for every additional T_reg/mm² (p = 0.05). Pro-fibrotic TGF-β1 was doubled in nonresponders (p = 0.032). On pathway analysis, decreased bFGF and increased PDGF-BB provide a possible mechanism for upregulation of TGF-β1. In conclusion, fibrosis is a plausible mechanism of pain complications and the adaptive immune response likely contributes to mitigation/prevention of complications and recovery in affected patients.

Statement of Significance

Polypropylene mesh improves anatomical outcomes in urogynecologic procedures, but is associated with complications, including pain and exposure through the vaginal epithelium. Mesh-induced pain is difficult to treat, and it is unclear why only half of women experience pain improvement after mesh removal. In this study, patient pain correlated with the presence of fibrosis and women with more T regulatory cells and lower TGF-β1 were more likely to have pain improvement following mesh removal. These findings implicate fibrosis as a mechanism of pain complications and suggest that the adaptive immune response may be responsible for prevention of complication and recovery. This improved understanding of how mesh can lead to pain moves us closer to the ultimate goal of preventing mesh complications.

中文翻译：

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T调节细胞和TGF-β1：网状并发症中宿主反应的预测因子。

聚丙烯网经常用于泌尿妇科手术；然而，大约 10% 的病例会出现疼痛和网状物暴露在阴道内。网片引起的疼痛，无论是否暴露，在 50% 的病例移除后仍然存在。慢性疼痛史预示着对网片移除的不良反应，但只有一小部分人有这种诊断。我们假设网片引起的疼痛与纤维化相关，并且无法改善炎症和纤维化宿主反应。接受网片去除的妇女被提供参与网状生物储存库。包括视觉模拟量表 (VAS) 骨盆疼痛评分在内的标准化问卷在入组时和移除后 6 个月完成。响应者被认为是那些具有≥13 mm VAS 改善的人。随机选择30个网状组织外植体进行分析。样品被标记为 CD8，_h ) 和 FoxP3 (T _regs )。使用定制的半定量测定法测量纤维周围胶原沉积（纤维化）。通过免疫测定法测定组织中 TGF-b1、bFGF、MCP-1、PDGF-BB 和 IGFBP-1 的浓度，并通过通路分析与阴道对照活检进行比较。VAS 疼痛评分与组织学纤维化程度相关。响应者有更多的 T _regs（7.8 对 0.3/mm ²，p  = 0.036），每增加一个 T _reg /mm ²，患者成为响应者的可能性是 1.6 倍（p  = 0.05）。无反应者中促纤维化 TGF-β1 增加了一倍（p = 0.032)。在通路分析中，减少的 bFGF 和增加的 PDGF-BB 提供了上调 TGF-β1 的可能机制。总之，纤维化是疼痛并发症的可能机制，适应性免疫反应可能有助于减轻/预防并发症和受影响患者的康复。

重要性声明

聚丙烯网片可改善泌尿妇科手术的解剖结果，但与并发症有关，包括疼痛和阴道上皮暴露。网片引起的疼痛难以治疗，目前尚不清楚为什么只有一半的女性在移除网片后疼痛有所改善。在这项研究中，患者疼痛与纤维化的存在相关，具有更多 T 调节细胞和较低 TGF-β1 的女性在移除网片后更可能有疼痛改善。这些发现暗示纤维化是疼痛并发症的一种机制，并表明适应性免疫反应可能是预防并发症和康复的原因。这种对网格如何导致疼痛的更好理解使我们更接近于防止网格并发症的最终目标。