Wingate Institute of Neurogastroenterology, Blizard Institute, Barts and The London School of Medicine and Dentistry, QMUL, London, UK.
Gastroenterology Department, Royal London Hospital, London, UK.
Neurogastroenterol Motil. 2019 Sep;31(9):e13667. doi: 10.1111/nmo.13667. Epub 2019 Jun 21.
Mucosal innervation in non-erosive reflux disease (NERD; pathological esophageal acid exposure, normal macroscopic mucosa) is clearly distinct from that of healthy volunteers (HV) and from patients with esophagitis or Barrett's esophagus: The nerves in NERD are situated much closer to the luminal surface of the mucosa. Patients with functional heartburn (FH) have a similar symptom profile to patients with NERD and indistinguishable macroscopic appearances. However, they have physiological acid exposure and no reflux-symptom association. The aim of our study was to delineate the position of esophageal mucosal nerve fibers in patients with FH and compare it with that in NERD and HV.
Distal esophageal biopsies from patients with FH were immunohistochemically stained for CGRP. CGRP-positive nerve fibers were identified, and their position relative to the lumen was determined. These results were compared to our previously published cohort of HV and NERD.
Eleven patients were included in the FH group with a mean age of 46 years (range 33-69); 7F:4M. Nine patients had visible nerve fibers. The location of the afferent nerve fibers in the distal esophageal mucosa (median of 22, range 10.4-28) was similar to the HV group (median 25.5) and significantly deeper than the superficial nerves seen in NERD (median 9.5).
The mucosal innervation pattern in FH is more alike that of healthy individuals than that of NERD, with afferent nerves lying deep in the mucosa, away from the luminal surface. This supports the theory that heartburn in FH has a distinct nociceptive pathophysiology.
非糜烂性反流病（NERD；病理性食管酸暴露，正常宏观黏膜）的黏膜神经支配明显不同于健康志愿者（HV）和食管炎或 Barrett 食管患者：NERD 中的神经更靠近黏膜的腔面。功能性烧心（FH）患者的症状谱与 NERD 患者相似，且宏观表现无区别。然而，他们存在生理性酸暴露，且无反流症状关联。我们的研究旨在描述 FH 患者食管黏膜神经纤维的位置，并与 NERD 和 HV 进行比较。
对 FH 患者的远端食管活检进行 CGRP 免疫组织化学染色。鉴定 CGRP 阳性神经纤维，并确定其相对于腔的位置。将这些结果与我们之前发表的 HV 和 NERD 队列进行比较。
FH 组纳入 11 例患者，平均年龄 46 岁（范围 33-69）；7 例女性，4 例男性。9 例患者可见神经纤维。远端食管黏膜中传入神经纤维的位置（中位数 22，范围 10.4-28）与 HV 组相似（中位数 25.5），明显深于 NERD 中可见的浅层神经（中位数 9.5）。
FH 中的黏膜神经支配模式与 HV 更相似，而与 NERD 不同，传入神经位于黏膜深部，远离腔面。这支持 FH 中烧心具有独特的伤害感受病理生理学理论。
