Wingate Institute of Neurogastroenterology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Centre for Tumour Biology, Barts Cancer Institute, Queen Mary University of London, London, UK.
Gastroenterology. 2017 Nov;153(5):1230-1239. doi: 10.1053/j.gastro.2017.07.017. Epub 2017 Jul 20.
BACKGROUND & AIMS: Little is known about the causes of heartburn in patients with gastro-esophageal reflux disease. Visible epithelial damage is seldom associated with symptom severity, evidenced by the significant symptom burden in patients with nonerosive reflux disease (NERD) compared with patients with erosive reflux disease (ERD) or Barrett's esophagus (BE). We studied the distribution of mucosal nerve fibers in patients with NERD, ERD, and BE, and compared the results with those of healthy subjects.
We performed a prospective study of 13 patients with NERD, 11 patients with ERD, and 16 patients with BE undergoing endoscopic evaluation in the United Kingdom or Greece. Biopsies were obtained from the proximal and distal esophageal mucosa of patients with NERD, from the distal esophageal mucosa of patients with ERD, and the distal-most squamous epithelium of patients with BE. These were examined for the presence and location of nerve fibers that reacted with a labeled antibody against calcitonin gene-related peptide (CGRP), a marker of nociceptive sensory nerves. The results were compared with those from 10 healthy volunteers (controls).
The distribution of CGRP-positive nerves did not differ significantly between the distal esophageal mucosa of controls (median, 25.5 cell layers to surface; interquartile range [IQR], 21.4-28.8) vs patients with ERD (median, 23 cell layers to surface; IQR, 16-27.5), or patients with BE (median, 21.5 cell layers to surface; IQR, 16.1-27.5). However, CGRP-positive nerves were significantly more superficial in mucosa from patients with NERD-both distal (median, 9.5 cell layers to surface; IQR, 1.5-13.3; P < .0001 vs ERD, BE, and controls) and proximal (median, 5.0 cell layers to surface; IQR, 2.5-9.3 vs median 10.4 cell layers to surface; IQR, 8.0-16.9; P = .0098 vs controls).
Proximal and distal esophageal mucosa of patients with NERD have more superficial afferent nerves compared with controls or patients with ERD or BE. Acid hypersensitivity in patients with NERD might be partially explained by the increased proximity of their afferent nerves to the esophageal lumen, and therefore greater exposure to noxious substances in refluxate.
人们对于胃食管反流病（GERD）患者烧心症状的病因知之甚少。可见的上皮损伤与症状严重程度很少相关，这一点从非糜烂性反流病（NERD）患者与糜烂性反流病（ERD）或 Barrett 食管（BE）患者相比，具有显著的症状负担中可以看出。我们研究了 NERD、ERD 和 BE 患者的黏膜神经纤维分布，并将结果与健康受试者进行了比较。
我们对英国和希腊的 13 名 NERD 患者、11 名 ERD 患者和 16 名 BE 患者进行了一项前瞻性研究。NERD 患者近端和远端食管黏膜、ERD 患者远端食管黏膜和 BE 患者远端最鳞状上皮均获得活检。这些组织均用于检查对降钙素基因相关肽（CGRP）标记抗体呈阳性反应的神经纤维的存在和位置，CGRP 是伤害感受性感觉神经的标志物。结果与 10 名健康志愿者（对照组）进行了比较。
对照组（中位数，25.5 个细胞层到表面；四分位距[IQR]，21.4-28.8）与 ERD 患者（中位数，23 个细胞层到表面；IQR，16-27.5）或 BE 患者（中位数，21.5 个细胞层到表面；IQR，16.1-27.5）的远端食管黏膜中 CGRP 阳性神经的分布无显著差异。然而，NERD 患者的黏膜中 CGRP 阳性神经明显更浅，无论是远端（中位数，9.5 个细胞层到表面；IQR，1.5-13.3；P <.0001 与 ERD、BE 和对照组相比）还是近端（中位数，5.0 个细胞层到表面；IQR，2.5-9.3 与中位数 10.4 个细胞层到表面；IQR，8.0-16.9；P =.0098 与对照组相比）。
与对照组或 ERD 或 BE 患者相比，NERD 患者的近端和远端食管黏膜有更多的感觉传入神经。NERD 患者的酸超敏可能部分解释为其传入神经更接近食管腔，因此更容易接触到反流物中的有害物质。
