Systemic lipopolysaccharide influences rectal sensitivity in rats: role of mast cells, cytokines, and vagus nerve.
Intraperitoneal lipopolysaccharide (LPS) produces somatic hyperalgesia, releases interleukin (IL)-1beta and tumor necrosis factor-alpha (TNF-alpha), and activates vagal afferents. The aim of this study was to evaluate the effect of peripheral LPS on rectal sensitivity and to specify the mechanisms involved. Abdominal muscle contractions were recorded in conscious rats equipped with intramuscular electrodes. Rectal distension (RD) was performed at various times after LPS or experimental treatments. In controls, RD significantly increased the number of abdominal contractions from a threshold volume of distension of 0.8 ml. At the lowest volume (0.4 ml), this number was increased after administration of LPS (3, 9, and 12 h later), recombinant human IL-1beta (from 3 to 9 h), recombinant bovine TNF-alpha (from 6 to 9 h), and BrX-537A (from 6 to 12 h), a mast cell degranulator. The effect of LPS was reduced by doxantrazole, Lys-D-Pro-Thr, and soluble recombinant TNF receptor. Vagotomy selectively amplified the response to LPS. We conclude that, in vivo, intraperitoneal LPS lowers visceral pain threshold (allodynia) through a mechanism involving mast cell degranulation and IL-1beta and TNF-alpha release and that the vagus nerve may exert a tonic protective role against LPS-induced rectal allodynia.
Coelho
A M
AM
Neuro-Gastroenterology and Nutrition Unit, Institut National de la Recherche Agronomique, 31931 Toulouse, France.
Fioramonti
J
J
Buéno
L
L
D000009:Abdominal Muscles / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002417:Cattle; D016207:Cytokines / Q000494:pharmacology*; D004926:Escherichia coli; D006801:Humans; D007274:Injections, Intraperitoneal; D007375:Interleukin-1 / Q000494:pharmacology; D053583:Interleukin-1beta; D007832:Lasalocid / Q000031:analogs & derivatives / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D012007:Rectum / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D013892:Thioxanthenes / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014628:Vagotomy; D014630:Vagus Nerve / Q000502:physiology*; D044004:Xanthones
D016207:Cytokines; D007375:Interleukin-1; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D011994:Recombinant Proteins; D013892:Thioxanthenes; D014409:Tumor Necrosis Factor-alpha; D044004:Xanthones; C056932:interleukin 1beta (193-195); C029086:bromolasalocid; C010134:doxantrazole; D007832:Lasalocid