ELSEVIER Neuroscience Letters 219 (1996) 147-150 NEUROSCI$C[ LETTERS Neurogenic inflammation in the gastrointestinal tract of the rat Holger Sann a'*, Maria Dux b, Michael Schemann a, G~ibor Jancs6 b aPhysiologisches lnstitut, Tieriirztliche Hochschule, Bischofsholer Damm 15/102, D-30173 Hannover, Germany bDepartment of Physiology, Albert Szent-Gyfrgyi Medical University, D6m tOr 10, H-6720 Szeged, Hungary Received 7 October 1996; revised version received 14 October 1996; accepted 14 October 1996 Abstract In contrast to the skin and some visceral organs the capability of capsaicin-sensitive sensory nerves of evoking an inflammatory response in the gastrointestinal tract is equivocal. We have therefore investigated the neurogenic plasma extravasation induced by local application of capsaicin to the stomach, duodenum, jejunum, ileum and colon of the rat. Permeable vessels were visualised histologi- cally with the vascular labelling technique using colloidal silver. In the smooth muscle layer of the small intestine, capsaicin elicited a 3- fold increase in the density of labelled blood vessels (diameter, 7-35 tim). Significant capsaicin-evoked plasma extravasation was also observed in the submucosa of the jejunum and ileum, and in the basal layer of the jejunal mucosa. Capsaicin-induced extravasation was not noted in the stomach and the colon. The data suggest the involvement of capsaicin-sensitive afferents in inflammatory processes in the rat small intestine. Keywords: Capsaicin; Plasma extravasation; Sensory fibres Direct stimulation or antidromic activation of capsaicin- sensitive sensory nerve endings produce an inflammatory response characterised by vasodilatation and plasma extra- vasation [7,14]. This neurogenic inflammation appears to be mediated by a local release of sensory neuropeptides such as substance P (SP) and calcitonin gene-related pep- tide (CGRP). In the skin, the vasodilatory response is mainly brought about by CGRP [3], whereas the increase in vascular permeability is mediated by SP [11]. Neuro- genic plasma extravasation occurs at postcapillary venules and is well described in many peripheral organs including the skin, the airways and the urogenital-tract [14]. However, experimental data on neurogenic inflamma- tion in the gastrointestinal tract are controversial. Some authors reported the lack of plasma extravasation in the entire gastrointestinal tract in response to either antidromic nerve stimulation or intravenous application of capsaicin or SP in rats and guinea-pigs [13,23]. In other studies, capsaicin induced vascular leakage only in the rat upper gastrointestinal tract (duodenum, stomach) [ 12,15]. * Corresponding author. Tel.: +49 511 8567449; fax: +49 511 8567687; e-mail: hsann@ physiology.tiho-hannover.de Recent data suggest an involvement of SP released from capsaicin-sensitive nerve fibres in inflammation of the ileum induced by Clostridium difficile [2,21]. In the mouse small intestine, the delayed-type hypersensitivity- induced plasma extravasation was also diminished by cap- saicin-pre-treatment [10]. These findings furnished only circumstantial evidence for the existence of neurogenic inflammatory mechanisms in the gut. We have therefore performed a systematic investigation of inflammatory responses evoked by local serosal application of capsaicin to the stomach, duodenum, jejunum, ileum and colon uti- lising the technique of vascular labelling which permits the direct visualisation of permeable blood vessels. Previous studies mentioned above have used the extravasation of Evans blue dye bound to serum albumin as a marker of plasma extravasation, and they did not investigate the vas- cular leakage in the different layers of the gut. Permeable fenestrated vessels in the mucosa might mask the stimulus- evoked plasma extravasation in other layers. We have therefore analysed vascular permeability in different layers using the labelling of permeable vessels by i.v. injected colloidal silver [4,8,9]. Colloidal silver escapes from the circulation through endothelial gaps of leaky blood vessels and gets stuck at the basement membrane 0304-3940/96/$12.00 © 1996 Elsevier Science Ireland Ltd. All rights reserved PII S0304-3940(96) 13181-5