Altered colorectal afferent function associated with TNBS-induced visceral hypersensitivity in mice
Altered colorectal afferent function associated with TNBS-induced visceral hypersensitivity in mice
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DOI：
10.1152/ajpgi.00257.2012
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发表时间：
2012-10-01
影响因子：
4.5
通讯作者：
Gebhart, G. F.
中科院分区：
文献类型：
--
作者：
Feng, Bin;La, Jun-Ho;Gebhart, G. F.
Feng B，La JH，Tanaka T，Schwartz ES，McMurray TP，Gebhart GF.小鼠中与TNBS诱导的内脏高敏感性相关的结肠直肠传入功能改变美国生理学杂志胃肠和肝脏生理学303：G817-G824，2012年。首次发表于2012年8月1日; doi：10.1152/ajpgi.00257.2012.-远端肠道的炎症通常与腹痛和超敏反应有关，但是否以及哪些结直肠传入纤维导致超敏反应尚不清楚。使用2，4，6-三硝基苯磺酸（TNBS）诱导的结肠炎小鼠模型，我们研究了结肠内TNBS后结直肠超敏反应以及结直肠和传入功能的相关变化。用TNBS或盐水结肠内处理C57 BL/6小鼠。在TNBS和盐水处理的（对照）小鼠中记录了8周内对结肠直肠扩张（15-60 mmHg）的内脏反应。在用TNBS或盐水处理的其他小鼠中，通过髓过氧化物酶测定和免疫组织学染色评估结肠直肠炎症。对TNBS和盐水处理的小鼠进行体外单纤维记录以评估结直肠传入功能。小鼠在TNBS治疗后第14天表现出显著的结肠直肠超敏反应，在第28天消退，在第56天没有再敏感。TNBS诱导了基于嗜中性粒细胞和巨噬细胞的结直肠炎症以及神经纤维的损失，所有这些都在第14-28天消退。单纤维记录显示，TNBS后第14天，牵拉敏感性结直肠传入神经的传入驱动净增加，而第14-28天，机械不敏感性传入神经（MIA）的比例减少。结肠内TNBS诱导的结直肠炎症与小鼠超敏反应的发展和恢复相关，这与牵张敏感性结直肠传入和MIA的致敏性的短暂增加和恢复相关。这些结果表明，炎症后结直肠超敏反应的发展和维持是由牵张敏感性结直肠传入神经的外周驱动和MIA的潜在贡献介导的。
Feng B, La JH, Tanaka T, Schwartz ES, McMurray TP, Gebhart GF. Altered colorectal afferent function associated with TNBS-induced visceral hypersensitivity in mice. Am J Physiol Gastrointest Liver Physiol 303: G817-G824, 2012. First published August 1, 2012; doi:10.1152/ajpgi.00257.2012.-Inflammation of the distal bowel is often associated with abdominal pain and hypersensitivity, but whether and which colorectal afferents contribute to the hypersensitivity is unknown. Using a mouse model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis, we investigated colorectal hypersensitivity following intracolonic TNBS and associated changes in colorectum and afferent functions. C57BL/6 mice were treated intracolonically with TNBS or saline. Visceromotor responses to colorectal distension (15-60 mmHg) were recorded over 8 wk in TNBS- and saline-treated (control) mice. In other mice treated with TNBS or saline, colorectal inflammation was assessed by myeloperoxidase assay and immunohistological staining. In vitro single-fiber recordings were conducted on both TNBS and saline-treated mice to assess colorectal afferent function. Mice exhibited significant colorectal hypersensitivity through day 14 after TNBS treatment that resolved by day 28 with no resensitization through day 56. TNBS induced a neutrophil-and macrophage-based colorectal inflammation as well as loss of nerve fibers, all of which resolved by days 14-28. Single-fiber recordings revealed a net increase in afferent drive from stretch-sensitive colorectal afferents at day 14 post-TNBS and reduced proportions of mechanically insensitive afferents (MIAs) at days 14-28. Intracolonic TNBS-induced colorectal inflammation was associated with the development and recovery of hypersensitivity in mice, which correlated with a transient increase and recovery of sensitization of stretch-sensitive colorectal afferents and MIAs. These results indicate that the development and maintenance of colorectal hypersensitivity following inflammation are mediated by peripheral drive from stretch-sensitive colorectal afferents and a potential contribution from MIAs.