Post-inflammatory colonic afferent sensitisation: different subtypes, different pathways and different time courses
Post-inflammatory colonic afferent sensitisation: different subtypes, different pathways and different time courses
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DOI：
10.1136/gut.2008.170811
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发表时间：
2009-10-01
期刊：
影响因子：
24.5
通讯作者：
Blackshaw, L. A.
中科院分区：
文献类型：
--
作者：
Hughes, P. A.;Brierley, S. M.;Blackshaw, L. A.
目的：肠易激综合征（IBS）患者在初始损伤愈合后很长时间内，肠道感染会引起超敏反应。三硝基苯磺酸 (TNBS) 在啮齿类动物中引起的结肠炎同样会导致迟发性维持性超敏反应，被视为 IBS 某些方面的模型。结肠和直肠具有复杂的感觉神经支配，包括内脏神经和骨盆神经中的五类机械敏感传入神经。它们的可塑性可能是肠易激综合症潜在机制的关键。因此，我们的目的是确定每种传入神经类别在炎症后内脏超敏反应的每个途径中的贡献。设计：经直肠施用 TNBS，并在 7（急性）或 28（恢复）天后对小鼠进行研究。使用附有骨盆或内脏神经的小鼠结肠直肠的体外制备物来检查个体结肠传入神经的机械敏感性。结果：结肠的轻度炎症急性明显，但在恢复阶段不存在。 TNBS 治疗没有改变治疗组之间五种传入神经类别的比例。在骨盆传入神经中，对照组和急性组小鼠对机械刺激的反应几乎没有或没有明显差异。然而，恢复后小鼠浆膜传入的机械敏感性显着增加，而其他亚型的反应则没有变化。浆膜和肠系膜内脏传入神经在急性期和恢复期均高度敏感。结论：机械感觉阈值高的结肠传入神经会导致炎症过敏，而阈值低的结肠传入神经则不会。骨盆传入神经主要在炎症恢复后参与，而内脏传入神经在炎症和恢复过程中都有涉及。
Objective: Intestinal infection evokes hypersensitivity in a subgroup of patients with irritable bowel syndrome (IBS) long after healing of the initial injury. Trinitrobenzene sulfonic acid (TNBS)-induced colitis in rodents likewise results in delayed maintained hypersensitivity, regarded as a model of some aspects of IBS. The colon and rectum have a complex sensory innervation, comprising five classes of mechanosensitive afferents in the splanchnic and pelvic nerves. Their plasticity may hold the key to underlying mechanisms in IBS. Our aim was therefore to determine the contribution of each afferent class in each pathway towards post-inflammatory visceral hypersensitivity.Design: TNBS was administered rectally and mice were studied after 7 (acute) or 28 (recovery) days. In vitro preparations of mouse colorectum with attached pelvic or splanchnic nerves were used to examine the mechanosensitivity of individual colonic afferents.Results: Mild inflammation of the colon was evident acutely which was absent at the recovery stage. TNBS treatment did not alter proportions of the five afferent classes between treatment groups. In pelvic afferents little or no difference in response to mechanical stimuli was apparent in any class between control and acute mice. However, major increases in mechanosensitivity were recorded from serosal afferents in mice after recovery, while responses from other subtypes were unchanged. Both serosal and mesenteric splanchnic afferents were hypersensitive at both acute and recovery stages.Conclusions: Colonic afferents with high mechanosensory thresholds contribute to inflammatory hypersensitivity, but not those with low thresholds. Pelvic afferents become involved mainly following recovery from inflammation, whereas splanchnic afferents are implicated during both inflammation and recovery.