Effect of nor-trimebutine on neuronal activation induced by a noxious stimulus or an acute colonic inflammation in the rat.
Nor-trimebutine is the main metabolite of trimebutine that is used in the treatment of patients with irritable bowel syndrome. Nor-trimebutine has a blocking activity on sodium channels and a potent local anesthetic effect. These properties were used to investigate the effect of nor-trimebutine on spinal neuronal activation induced by models of noxious somato-visceral stimulus and acute colonic inflammation. Nor-trimebutine was administered in rats either subcutaneously 30 min before intraperitoneal administration of acetic acid or intracolonically 30 min before intracolonic infusion of trinitrobenzenesulfonic acid. Abdominal contractions were counted for 1 h as a marker of abdominal pain. c-fos expression was used as a marker of neuronal activation and revealed by immunohistochemistry 1h after intraperitoneal acetic acid injection and 2 h after colonic inflammation. Nor-trimebutine decreased Fos expression in the thoraco-lumbar (peritoneal irritation) and lumbo-sacral (colonic inflammation) spinal cord in laminae I, IIo V, VII and X. This effect was also observed in the sacral parasympathetic nucleus after colonic inflammation. Nor-trimebutine induced a significant decrease of abdominal contractions following intraperitoneal acetic acid injection. These data may explain the effectiveness of trimebutine in the therapy of abdominal pain in the irritable bowel syndrome.
Groupe d'Etudes du Stress et des Interactions Neuro-Digestives (GESIND; EA3744), France.
Valérie
V
Sinniger
Patrick
P
Mouchet
Bruno
B
Bonaz
D015746:Abdominal Pain / Q000188:drug therapy; D019342:Acetic Acid / Q000633:toxicity; D000779:Anesthetics, Local / Q000627:therapeutic use*; D000818:Animals; D003092:Colitis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D014287:Trimebutine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity; D017833:Visceral Afferents / Q000187:drug effects
D000779:Anesthetics, Local; D016760:Proto-Oncogene Proteins c-fos; D014302:Trinitrobenzenesulfonic Acid; D019342:Acetic Acid; D014287:Trimebutine