Mast cell-dependent excitation of visceral-nociceptive sensory neurons in irritable bowel syndrome
Mast cell-dependent excitation of visceral-nociceptive sensory neurons in irritable bowel syndrome
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DOI：
10.1053/j.gastro.2006.11.039
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发表时间：
2007-01-01
期刊：
影响因子：
29.4
通讯作者：
Corinaldesi, Roberto
中科院分区：
文献类型：
--
作者：
Barbara, Giovanni;Wang, Bingxian;Corinaldesi, Roberto
背景与目的：肠肥大细胞浸润可能参与肠易激综合征（IBS）患者腹痛的发生。然而，其潜在机制尚不清楚。我们评估了肠易激综合征患者结肠粘膜释放的肥大细胞介质对体外大鼠感觉神经元激活的影响。方法：采用定量免疫荧光法和免疫酶法测定结肠肥大细胞浸润和介质释放情况。研究了粘膜介质对大鼠肠系膜感觉神经放电和背根神经节Ca2+动员的影响。结果：IBS患者而非对照组的介质显著增强肠系膜神经放电（14.7 +/- 3.2 imp/sec vs 2.8 +/- 1.5 imp/sec; P < 0.05），刺激背根神经节神经元Ca2+的动员（29% +/- 4% vs 11% +/- 4%; P < 0.05）。平均而言，64%的背根神经节对介质反应是辣椒素敏感的，已知可以介导伤害感觉。组胺和胰蛋白酶主要分布于粘膜肥大细胞。ibs依赖性神经放电和Ca2+动员与肥大细胞占据的结肠固有层面积相关（r = 0.74, P < 0.01, r = 0.78, P < 0.01）。组胺H、受体阻断和丝氨酸蛋白酶失活可抑制ibs依赖性背根神经节的兴奋（抑制率分别为51.7%,P < 0.05和74.5%,P < 0.05）。结论：肠易激综合征患者的粘膜肥大细胞介质可刺激大鼠内脏感觉神经。这些结果为肠易激综合征内脏超敏反应的机制提供了新的见解。
Background & Aims: Intestinal mast cell infiltration may participate to abdominal pain in irritable bowel syndrome (IBS) patients. However, the underlying mechanisms remain unknown. We assessed the effect of mast cell mediators released from the colonic mucosa of IBS patients on the activation of rat sensory neurons in vitro. Methods: Colonic mast cell infiltration and mediator release were assessed with quantitative immunoflorescence and immunoenzymatic assays. The effect of mucosal mediators was tested on mesenteric sensory nerve firing and Ca2+ mobilization in dorsal root ganglia in rats. Results: Mediators from IBS patients, but not controls, markedly enhanced the firing of mesenteric nerves (14.7 +/- 3.2 imp/sec vs 2.8 +/- 1.5 imp/sec; P < .05) and stimulated mobilization of Ca2+ in dorsal root ganglia neurons (29% +/- 4% vs 11% +/- 4%; P < .05). On average, 64% of dorsal root ganglia responsive to mediators were capsaicin-sensitive, known to mediate nociception. Histamine and tryptase were mainly localized to mucosal mast cells. IBS-dependent nerve firing and Ca2+ mobilization were correlated with the area of the colonic lamina propria occupied by mast cells (r = 0.74; P < .01, and r = 0.78; P < .01, respectively). IBS-dependent excitation of dorsal root ganglia was inhibited by histamine H, receptor blockade and serine protease inactivation (inhibition of 51.7%; P < .05 and 74.5%; P < .05; respectively). Conclusions: Mucosal mast cell mediators from IBS patients excite rat nociceptive visceral sensory nerves. These results provide new insights into the mechanism underlying visceral hypersensitivity in IBS.