Lee Robert H, Korsapati Hariprasad, Bhalla Vikas, Varki Nissi, Mittal Ravinder K
Division of Gastroenterology, University of California Irvine, Irvine, CA, USA.
Division of Gastroenterology, University of California, San Diego, San Diego, CA, USA.
J Neurogastroenterol Motil. 2016 Jul 30;22(3):436-43. doi: 10.5056/jnm15166.
BACKGROUND/AIMS: Transient receptor potential vanilloid-1 (TRPV1) is a candidate for mediating acid-induced symptoms in the esophagus. We conducted studies to determine if the presence of acid in the mucosa/submucosa and direct activation of TRPV1 by capsaicin elicited symptoms in normal healthy subjects. We also studied the presence of TRPV1 receptors in the esophagus.
Unsedated endoscopy was performed on healthy subjects with no symptoms. Using a sclerotherapy needle, normal saline (pH 2.0-7.5) was injected into the mucosa/submucosa, 5 cm above the Z line. In a separate group of healthy subjects, injection of capsaicin and vehicle was also studied. Quality of symptoms was reported using the McGill Pain Questionnaire, and symptom intensity using the visual analogue scale (VAS). Immunohistochemistry was performed on 8 surgical esophagus specimens using TRPV1 antibody.
Acid injection either did not elicit or elicited mild symptoms in subjects at all pH solutions. Capsaicin but not the vehicle elicited severe heartburn/chest pain in all subjects. Mean VAS for capsaicin was 91 ± 3 and symptoms lasted for 25 ± 1 minutes. Immunohistochemistry revealed a linear TRPV1 staining pattern between the epithelial layer and the submucosa that extended into the papillae. Eighty-five percent of papillae stained positive for TRPV1 with a mean 1.1 positive papillae per high-powered field.
The mechanism of acid-induced heartburn and chest pain is not the simple interaction of hydrogen ions with afferents located in the esophageal mucosa and submucosa. TRPV1 receptors are present in the lamina propria and their activation induces heartburn and chest pain.
背景/目的：瞬时受体电位香草酸亚型1（TRPV1）是介导食管酸诱导症状的一个候选因素。我们开展研究以确定黏膜/黏膜下层中酸的存在以及辣椒素对TRPV1的直接激活是否会在正常健康受试者中引发症状。我们还研究了食管中TRPV1受体的存在情况。
对无症状的健康受试者进行非镇静状态下的内镜检查。使用硬化治疗针，将生理盐水（pH 2.0 - 7.5）注入Z线以上5 cm处的黏膜/黏膜下层。在另一组健康受试者中，还研究了辣椒素和赋形剂的注射情况。使用麦吉尔疼痛问卷报告症状的性质，使用视觉模拟量表（VAS）报告症状的强度。使用TRPV1抗体对8个手术切除的食管标本进行免疫组织化学检查。
在所有pH值溶液的受试者中，注射酸要么未引发症状，要么引发轻微症状。辣椒素而非赋形剂在所有受试者中引发了严重的烧心/胸痛。辣椒素的平均VAS为91±3，症状持续25±1分钟。免疫组织化学显示，在上皮层和黏膜下层之间存在线性的TRPV1染色模式，并延伸至乳头。85%的乳头TRPV1染色呈阳性，每个高倍视野平均有1.1个阳性乳头。
酸诱导的烧心和胸痛机制并非氢离子与位于食管黏膜和黏膜下层的传入神经的简单相互作用。TRPV1受体存在于固有层，其激活会诱发烧心和胸痛。
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