PDF(Pubmed)
Abstract：
BACKGROUND: Serotonin receptor 2B (5-HT2B receptor) plays a critical role in many chronic pain conditions. The possible involvement of the 5-HT2B receptor in the altered gut sensation of irritable bowel syndrome with diarrhea (IBS-D) was investigated in the present study.
OBJECTIVE: To investigate the possible involvement of 5-HT2B receptor in the altered gut sensation in rat model and patients with IBS-D.
METHODS: Rectosigmoid biopsies were collected from 18 patients with IBS-D and 10 patients with irritable bowel syndrome with constipation who fulfilled the Rome IV criteria and 15 healthy controls. The expression level of the 5-HT2B receptor in colon tissue was measured using an enzyme-linked immunosorbent assay and correlated with abdominal pain scores. The IBS-D rat model was induced by intracolonic instillation of acetic acid and wrap restraint. Alterations in visceral sensitivity and 5-HT2B receptor and transient receptor potential vanilloid type 1 (TRPV1) expression were examined following 5-HT2B receptor antagonist administration. Changes in visceral sensitivity after administration of the TRPV1 antagonist were recorded.
RESULTS: Here, we observed greater expression of the 5-HT2B receptor in the colonic mucosa of patients with IBS-D than in that of controls, which was correlated with abdominal pain scores. Intracolonic instillation of acetic acid and wrap restraint induced obvious chronic visceral hypersensitivity and increased fecal weight and fecal water content. Exogenous 5-HT2B receptor agonist administration increased visceral hypersensitivity, which was alleviated by successive administration of a TRPV1 antagonist. IBS-D rats receiving the 5-HT2B receptor antagonist exhibited inhibited visceral hyperalgesia.Moreover, the percentage of 5-HT2B receptor-immunoreactive (IR) cells surrounded by TRPV1-positive cells (5-HT2B receptor I+) and total 5-HT2B receptor IR cells (5-HT2B receptor IT) in IBS-D rats was significantly reduced by the administration of a 5-HT2B receptor antagonist.
CONCLUSIONS: Our finding that increased expression of the 5-HT2B receptor contributes to visceral hyperalgesia by inducing TRPV1 expression in IBS-D patients provides important insights into the potential mechanisms underlying IBS-D-associated visceral hyperalgesia.
OBJECTIVE: To investigate the possible involvement of 5-HT2B receptor in the altered gut sensation in rat model and patients with IBS-D.
METHODS: Rectosigmoid biopsies were collected from 18 patients with IBS-D and 10 patients with irritable bowel syndrome with constipation who fulfilled the Rome IV criteria and 15 healthy controls. The expression level of the 5-HT2B receptor in colon tissue was measured using an enzyme-linked immunosorbent assay and correlated with abdominal pain scores. The IBS-D rat model was induced by intracolonic instillation of acetic acid and wrap restraint. Alterations in visceral sensitivity and 5-HT2B receptor and transient receptor potential vanilloid type 1 (TRPV1) expression were examined following 5-HT2B receptor antagonist administration. Changes in visceral sensitivity after administration of the TRPV1 antagonist were recorded.
RESULTS: Here, we observed greater expression of the 5-HT2B receptor in the colonic mucosa of patients with IBS-D than in that of controls, which was correlated with abdominal pain scores. Intracolonic instillation of acetic acid and wrap restraint induced obvious chronic visceral hypersensitivity and increased fecal weight and fecal water content. Exogenous 5-HT2B receptor agonist administration increased visceral hypersensitivity, which was alleviated by successive administration of a TRPV1 antagonist. IBS-D rats receiving the 5-HT2B receptor antagonist exhibited inhibited visceral hyperalgesia.Moreover, the percentage of 5-HT2B receptor-immunoreactive (IR) cells surrounded by TRPV1-positive cells (5-HT2B receptor I+) and total 5-HT2B receptor IR cells (5-HT2B receptor IT) in IBS-D rats was significantly reduced by the administration of a 5-HT2B receptor antagonist.
CONCLUSIONS: Our finding that increased expression of the 5-HT2B receptor contributes to visceral hyperalgesia by inducing TRPV1 expression in IBS-D patients provides important insights into the potential mechanisms underlying IBS-D-associated visceral hyperalgesia.
摘要：
背景：5-羟色胺受体2B（5-HT2B受体）在许多慢性疼痛病症中起关键作用。本研究调查了5-HT2B受体可能参与腹泻型肠易激综合征（IBS-D）的肠道感觉改变。
目的：探讨5-HT2B受体在大鼠模型和IBS-D患者肠道感觉改变中的可能作用。
方法：收集符合罗马IV标准的18例IBS-D患者和10例便秘型肠易激综合征患者和15例健康对照的直肠乙状结肠活检。使用酶联免疫吸附测定法测量结肠组织中5-HT2B受体的表达水平，并与腹痛评分相关。IBS-D年夜鼠模子采取结肠内滴注乙酸和包裹克制办法。在施用5-HT2B受体拮抗剂后，检查了内脏敏感性和5-HT2B受体以及1型瞬时受体电位香草素（TRPV1）表达的变化。记录施用TRPV1拮抗剂后内脏敏感性的变化。
结果：这里，我们观察到IBS-D患者结肠黏膜中5-HT2B受体的表达高于对照组,与腹痛评分相关。结肠内滴注乙酸和包裹克制惹起明显的慢性内脏高敏感，增长粪便重量和粪便含水量。外源性5-HT2B受体激动剂给药增加内脏超敏反应，通过连续施用TRPV1拮抗剂来缓解。接受5-HT2B受体拮抗剂的IBS-D大鼠表现出抑制的内脏痛觉过敏。此外，通过施用5-HT2B受体拮抗剂,IBS-D大鼠中被TRPV1阳性细胞(5-HT2B受体I+)和总5-HT2B受体IR细胞(5-HT2B受体IT)包围的5-HT2B受体免疫反应性(IR)细胞的百分比显著降低。
结论：我们的发现5-HT2B受体的表达增加通过在IBS-D患者中诱导TRPV1表达而导致内脏痛觉过敏，为IBS-D相关内脏痛觉过敏的潜在机制提供了重要见解。
目的：探讨5-HT2B受体在大鼠模型和IBS-D患者肠道感觉改变中的可能作用。
方法：收集符合罗马IV标准的18例IBS-D患者和10例便秘型肠易激综合征患者和15例健康对照的直肠乙状结肠活检。使用酶联免疫吸附测定法测量结肠组织中5-HT2B受体的表达水平，并与腹痛评分相关。IBS-D年夜鼠模子采取结肠内滴注乙酸和包裹克制办法。在施用5-HT2B受体拮抗剂后，检查了内脏敏感性和5-HT2B受体以及1型瞬时受体电位香草素（TRPV1）表达的变化。记录施用TRPV1拮抗剂后内脏敏感性的变化。
结果：这里，我们观察到IBS-D患者结肠黏膜中5-HT2B受体的表达高于对照组,与腹痛评分相关。结肠内滴注乙酸和包裹克制惹起明显的慢性内脏高敏感，增长粪便重量和粪便含水量。外源性5-HT2B受体激动剂给药增加内脏超敏反应，通过连续施用TRPV1拮抗剂来缓解。接受5-HT2B受体拮抗剂的IBS-D大鼠表现出抑制的内脏痛觉过敏。此外，通过施用5-HT2B受体拮抗剂,IBS-D大鼠中被TRPV1阳性细胞(5-HT2B受体I+)和总5-HT2B受体IR细胞(5-HT2B受体IT)包围的5-HT2B受体免疫反应性(IR)细胞的百分比显著降低。
结论：我们的发现5-HT2B受体的表达增加通过在IBS-D患者中诱导TRPV1表达而导致内脏痛觉过敏，为IBS-D相关内脏痛觉过敏的潜在机制提供了重要见解。
