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Am J Physiol Gastrointest Liver Physiol 292: G1213-G1220, 2007. First published January 4, 2007; doi:10.1152/ajpgi.00267.2006
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NEUROREGULATION AND MOTILITY

Vagal modulation of intestinal afferent sensitivity to systemic LPS in the rat

C. Y. Liu,1 M. H. Mueller,2 D. Grundy,3 and M. E. Kreis2

1Institute of Physiology, School of Medicine, Shandong University, Shandong, China; 2Department of Surgery, Ludwig-Maximilians University, Munich, Germany; and 3Department of Biomedical Sciences, University of Sheffield, Sheffield, United Kingdom

Submitted 19 June 2006 ; accepted in final form 29 December 2006

The central nervous system modulates inflammation in the gastrointestinal tract via efferent vagal pathways. We hypothesized that these vagal efferents receive synaptic input from vagal afferents, representing an autonomic feedback mechanism. The consequence of this vagovagal reflex for afferent signal generation in response to LPS was examined in the present study. Different modifications of the vagal innervation or sham procedures were performed in anesthetized rats. Extracellular mesenteric afferent nerve discharge and systemic blood pressure were recorded in vivo before and after systemic administration of LPS (6 mg/kg iv). Mesenteric afferent nerve discharge increased dramatically following LPS, which was unchanged when vagal efferent traffic was eliminated by acute vagotomy. In chronically vagotomized animals, to eliminate both vagal afferent and efferent traffic, the increase in afferent firing 3.5 min after LPS was reduced to 3.2 ± 2.5 impulses/s above baseline compared with 42.2 ± 2.0 impulses/s in controls (P < 0.001). A similar effect was observed following perivagal capsaicin, which was used to eliminate vagal afferent traffic only. LPS also caused a transient hypotension (<10 min), a partial recovery, and then persistent hypertension that was exacerbated by all three procedures. Mechanosensitivity was increased 15 min following LPS but had recovered at 30 min in all subgroups except for the chronic vagotomy group. In conclusion, discharge in capsaicin-sensitive mesenteric vagal afferents is augmented following systemic LPS. This activity, through a vagovagal pathway, helps to attenuate the effects of septic shock. The persistent hypersensitivity to mechanical stimulation after chronic vagal denervation suggests that the vagus exerts a regulatory influence on spinal afferent sensitization following LPS.

autonomic innervation; electrophysiology; mesenteric; vagus nerve; visceral hypersensitivity; lipopolysaccharide



Address for reprint requests and other correspondence: M. E. Kreis, Ludwig-Maximilians Univ., Univ. Hospital Grosshadern, Marchioninistrasse 15, D-81377 Munich, Germany (e-mail: martin.kreis{at}med.uni-muenchen.de)







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