Brain interleukin-1beta and tumor necrosis factor-alpha are involved in lipopolysaccharide-induced delayed rectal allodynia in awake rats.
Recently, we have developed a model of delayed (12 h) increase in sensitivity (allodynia) to rectal distension (RD) induced by intraperitoneal lipopolysaccharide (LPS) in awake rats. Thus, we examined whether central interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) are involved in LPS response. Abdominal contractions (criterion of visceral pain) were recorded in rats equipped with intramuscular electrodes. RDs were performed at various times after pharmacological treatments. RD induced abdominal contractions from a threshold volume of distension of 0.8 ml. At lowest volume (0.4 ml), this number was significantly increased 12 h after LPS. Intracerebroventricular (i.c.v.) injection of IL-1 receptor antagonist, IL-1beta converting enzyme inhibitor or recombinant human TNF-alpha soluble receptor reduced LPS-induced increase of abdominal contractions at 0.4 ml volume of distension. When injected i.c.v., recombinant human IL-1beta and recombinant bovine TNF-alpha reproduced LPS response at 9 and 12 h and at 6 and 9 h, respectively. These data suggest that IL-1beta and TNF-alpha act centrally to induce delayed rectal hypersensitivity and that central release of these cytokines is responsible of LPS-induced delayed (12 h) rectal allodynia.
Coelho
A
A
Institut National de la Recherche Agronomique, Neurogastroenterology and Nutrition Unit, Toulouse, France.
Fioramonti
J
J
Bueno
L
L
D000818:Animals; D001921:Brain / Q000378:metabolism*; D003243:Consciousness; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004576:Electromyography; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000378:metabolism* / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009619:Nociceptors / Q000502:physiology; D010147:Pain Measurement; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D012007:Rectum / Q000294:innervation* / Q000502:physiology*; D015843:Serpins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology; D014764:Viral Proteins
D015853:Cysteine Proteinase Inhibitors; D007375:Interleukin-1; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D015843:Serpins; D014409:Tumor Necrosis Factor-alpha; D014764:Viral Proteins; C074641:interleukin-1beta-converting enzyme inhibitor