无髓鞘C纤维上的TRPV1受体介导大鼠结肠炎诱导的盆腔传入神经纤维致敏。

TRPV1 receptors on unmyelinated C-fibres mediate colitis-induced sensitization of pelvic afferent nerve fibres in rats.

作者信息

De Schepper H U, De Winter B Y, Van Nassauw L, Timmermans J-P, Herman A G, Pelckmans P A, De Man J G

机构信息

Laboratory of Experimental Medicine and Pediatrics, Division of Gastroenterology, Faculty of Medicine, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium.

出版信息

J Physiol. 2008 Nov 1;586(21):5247-58. doi: 10.1113/jphysiol.2008.159731. Epub 2008 Aug 28.

Abstract

Patients with inflammatory bowel disease often suffer from gastrointestinal motility and sensitivity disorders. The aim of the current study was to investigate the role of transient receptor potential of the vanilloid type 1 (TRPV1) receptors in the pathophysiology of colitis-induced pelvic afferent nerve sensitization. Trinitrobenzene sulphate (TNBS) colitis (7.5 mg, 30% ethanol) was induced in Wistar rats 72 h prior to the experiment. Single-fibre recordings were made from pelvic nerve afferents in the decentralized S1 dorsal root. Fibres responding to colorectal distension (CRD) were identified in controls and rats with TNBS colitis. The effect of the TRPV1 antagonist N-(4-tertiarybutylphenyl)-4-(3-chlorophyridin-2-yl)tetrahydropyrazine-1(2H)carboxamide (BCTC; 0.25-5 mg kg(-1)) or its vehicle (hydroxypropyl-beta-cyclodextrin) was tested on the afferent response to repetitive distensions (60 mmHg). Immunocytochemical staining of TRPV1 and NF200, a marker for A-fibre neurons, was performed in the dorsal root ganglia L6-S1. TNBS colitis significantly increased the response to colorectal distension of pelvic afferent C-fibres. BCTC did not significantly affect the C-fibre response in controls, but normalized the sensitized response in rats with colitis. TNBS colitis increased the spontaneous activity of C-fibres, an effect which was insensitive to administration of BCTC. TNBS colitis had no effect on Adelta-fibres, nor was their activity modulated by BCTC. TNBS colitis caused an immunocytochemical up-regulation of TRPV1 receptors in the cell bodies of pelvic afferent NF200 negative neurons. TRPV1 signalling mediates the colitis-induced sensitization of pelvic afferent C-fibres to CRD, while Adelta-fibres are neither sensitized by colitis nor affected by TRPV1 inhibition.

摘要

炎症性肠病患者常伴有胃肠动力和敏感性障碍。本研究旨在探讨1型香草酸类瞬时受体电位(TRPV1)受体在结肠炎诱导的盆腔传入神经致敏病理生理过程中的作用。实验前72小时,用三硝基苯磺酸(TNBS)(7.5毫克,30%乙醇)诱导Wistar大鼠患结肠炎。在去传入神经支配的S1背根记录盆腔神经传入纤维的单纤维活动。在对照组和TNBS结肠炎大鼠中识别对结直肠扩张(CRD)有反应的纤维。测试TRPV1拮抗剂N-(4-叔丁基苯基)-4-(3-氯吡啶-2-基)四氢吡嗪-1(2H)甲酰胺(BCTC;0.25 - 5毫克/千克)或其溶剂(羟丙基-β-环糊精)对重复扩张(60毫米汞柱)传入反应的影响。在L6 - S1背根神经节进行TRPV1和A纤维神经元标志物NF200的免疫细胞化学染色。TNBS结肠炎显著增加了盆腔传入C纤维对结直肠扩张的反应。BCTC对对照组C纤维反应无显著影响,但使结肠炎大鼠的致敏反应恢复正常。TNBS结肠炎增加了C纤维的自发活动,该效应不受BCTC给药的影响。TNBS结肠炎对Aδ纤维无影响,其活动也不受BCTC调节。TNBS结肠炎导致盆腔传入NF200阴性神经元胞体中TRPV1受体的免疫细胞化学上调。TRPV1信号传导介导了结肠炎诱导的盆腔传入C纤维对CRD的致敏,而Aδ纤维既不被结肠炎致敏也不受TRPV1抑制的影响。

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