Toneman Masja Karina, Marianne Faas Priscilla Pauline, Christian Antoine Marie Gielen Maurits Johan, Carotti Valentina, Adriana van Oirschot Anne Elisa, Maria Mangnus Judith Petronella, Wintjens Anne, Mihl Casper, Huige Josephine, Grosser Bianca, Blussé van Oud-Alblas Marjolein, Willem van Dongen Koen, Bouvy Nicole Dorine, van Goor Harry, Keszthelyi Daniel, Grabsch Heike Irmgard, Gerardus Ten Broek Richard Peter
Surgery Department, Radboudumc, Nijmegen, the Netherlands.
Surgery Department, Radboudumc, Nijmegen, the Netherlands.
EBioMedicine. 2025 Jun;116:105746. doi: 10.1016/j.ebiom.2025.105746. Epub 2025 May 23.
Chronic abdominal pain affects 10-20% of all patients following abdominal surgery, with adhesions as a predominant cause. However, the biological mechanisms underlying adhesion-related pain are not fully elucidated. This study aimed to establish the morphological and molecular phenotype of adhesions in patients with and without chronic postoperative abdominal pain.
In this case-control study, biopsies of adhesions were obtained from patients with chronic postoperative abdominal pain (related to adhesions on cineMRI) and controls without pain, from two tertiary care and one secondary care hospital. Quantitative histological analysis of haematoxylin and eosin-stained sections was performed, while immunohistochemical (IHC) markers for nerve tissue (S100, calretinin and synaptophysin) were quantified through image analysis. RNA expression of genes (TRPV1, BDNF, TAC1, TACR1, NGF) was measured using real time quantitative polymerase chain reaction (RT-qPCR). Controls were matched to cases by sex, age, and prior surgery, accepting small variations due to patient availability. An independent two-sided t-test was used to detect differences in IHC and RT-qPCR analysis between groups.
Adhesions from 31 patients with pain were compared to those from 31 patients without pain, consisting of 48% connective tissue and 41% adipose tissue. Immunohistochemical analysis revealed increased nerve tissue in patients with pain (S100: median 597 ppm (range 92.2-3223.2 ppm) vs 151 ppm (range 15.2-1683.8 ppm) p < 0.001; calretinin: median 463 ppm (range 72.7-2996.5 ppm) vs 275 ppm (range 35.3-3194.8 ppm) p = 0.040). NGF showed a higher mRNA expression in adhesions from patients with pain compared to controls (p = 0.012).
This study suggests a distinct morphological and molecular phenotype of adhesions in patients experiencing adhesion-related pain, providing insights into underlying mechanisms.
Veni grant from The Dutch Governmental Organisation for Health Research and Development (ZonMw grant number 91619035).
慢性腹痛影响10% - 20%的腹部手术后患者，粘连是主要原因。然而，粘连相关疼痛的生物学机制尚未完全阐明。本研究旨在确定有和没有慢性术后腹痛的患者粘连的形态学和分子表型。
在这项病例对照研究中，从两家三级护理医院和一家二级护理医院的慢性术后腹痛患者（与电影磁共振成像上的粘连相关）和无疼痛的对照患者中获取粘连组织活检样本。对苏木精和伊红染色切片进行定量组织学分析，同时通过图像分析对神经组织的免疫组织化学（IHC）标记物（S100、钙视网膜蛋白和突触素）进行定量。使用实时定量聚合酶链反应（RT-qPCR）测量基因（TRPV1、BDNF、TAC1、TACR1、NGF）的RNA表达。根据性别、年龄和既往手术情况将对照与病例进行匹配，因患者可及性接受小的差异。使用独立双侧t检验检测两组之间IHC和RT-qPCR分析的差异。
将31例疼痛患者的粘连与31例无疼痛患者的粘连进行比较，粘连组织中结缔组织占48%，脂肪组织占41%。免疫组织化学分析显示，疼痛患者的神经组织增加（S100：中位数597 ppm（范围92.2 - 3223.2 ppm）对151 ppm（范围15.2 - 1683.8 ppm），p < 0.001；钙视网膜蛋白：中位数463 ppm（范围72.7 - 2996.5 ppm）对275 ppm（范围35.3 - 3194.8 ppm），p = 0.040）。与对照组相比，疼痛患者粘连组织中NGF的mRNA表达更高（p = 0.012）。
本研究提示粘连相关疼痛患者的粘连具有独特的形态学和分子表型，为潜在机制提供了见解。
荷兰卫生研究与发展政府组织的Veni资助（ZonMw资助编号91619035）。
