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Effect of nor-trimebutine on neuronal activation induced by a noxious stimulus or an acute colonic inflammation in the rat.

Abstract : 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.
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https://www.hal.inserm.fr/inserm-00388054
Contributor : Valérie Sinniger <>
Submitted on : Friday, July 31, 2009 - 11:12:02 AM
Last modification on : Tuesday, August 4, 2009 - 5:26:18 PM

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Valérie Sinniger, Patrick Mouchet, Bruno Bonaz. Effect of nor-trimebutine on neuronal activation induced by a noxious stimulus or an acute colonic inflammation in the rat.. Life Sciences, Elsevier, 2005, 77 (23), pp.2927-41. ⟨10.1016/j.lfs.2005.05.030⟩. ⟨inserm-00388054⟩

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