Lipopolysaccharide-induced changes in mesenteric afferent sensitivity of rat jejunum in vitro: role of prostaglandins.
Bacterial translocation across the intestinal mucosal barrier leads to a macrophage-mediated inflammatory response, visceral hyperalgesia, and ileus. Our aim was to examine how mediators released into mesenteric lymph following LPS treatment influence intestinal afferent sensitivity and the role played by prostanoids in any sensitization. Intestinal lymph was collected from awake rats following treatment with either saline or LPS (5 mg/kg ip). Extracellular multiunit afferent recordings were made from paravascular mesenteric nerve bundles supplying the rat jejunum in vitro following arterial administration of control lymph, LPS lymph, and LPS. Mesenteric afferent discharge increased significantly after LPS lymph compared with control lymph. Peak discharge occurred within 2 min and remained elevated for 5 to 8 min. This response was attenuated by pretreatment with naproxen (10 microM), and restored upon addition of prostaglandin E(2) (5 microM) in the presence of naproxen, but AH6809 (5 microM), an EP(1)/EP(2) receptor(s) antagonist, failed to decrease the magnitude of LPS lymph-induced response. LPS itself also stimulated mesenteric afferent discharge but was unaffected by naproxen. TNF-alpha was significantly increased in LPS lymph compared with control lymph (1,583 +/- 197 vs. 169 +/- 38 pg/ml, P < 0.01) but exogenous TNF-alpha failed to evoke any afferent nerve discharge. We concluded that inflammatory mediators released from the gut into mesenteric lymph during endotoxemia have a profound effect on afferent discharge. These mediators influence afferent firing via the release of local prostaglandins.
Wang
B
B
Dept. of Biomedical Science, University of Sheffield, Sheffield S10 2TN, UK.
Glatzle
J
J
Mueller
M H
MH
Kreis
M
M
Enck
P
P
Grundy
D
D
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D066298:In Vitro Techniques; D007583:Jejunum / Q000294:innervation*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008198:Lymph Nodes / Q000294:innervation; D008297:Male; D009288:Naproxen / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology*; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D044004:Xanthones / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D014409:Tumor Necrosis Factor-alpha; D044004:Xanthones; C053876:6-isopropoxy-9-oxoxanthene-2-carboxylic acid; D009288:Naproxen; D015232:Dinoprostone