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

Abstract

To cite this version: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) EFFECT OF NOR-TRIMEBUTINE ON NEURONAL ACTIVATION INDUCED BY A NOXIOUS STIMULUS OR AN ACUTE COLONIC INFLAMMATION IN THE RATValérie Sinniger(1,2), Patrick Mouchet (1), and Bruno Bonaz (1,2) ABSTRACTNor-trimebutine is the main metabolite of trimebutine which is used in the treatment of patients with irritable bowel syndrome. Nor-trimebutine has a blocking activity on sodium channel and a potent local anaesthetic effect. These properties were used to investigate the effect of nortrimebutine on spinal neuronal activation induced by models of noxious somato-visceral stimulus and acute colonic inflammation. Nor-trimebutine was administered subcutaneously in rats 30 min

A novel orally administered trimebutine compound (GIC‐1001) is anti‐nociceptive and features peripheral opioid agonistic activity and Hydrogen Sulphide‐releasing capacity in mice

“…This active metabolite acts as a blocker of sodium channels activity and also has a potent local anaesthetic effect (Roman et al., ). In rats, it decreases c‐Fos expression in the thoracolumbar and lumbo‐sacral spinal cord in laminae I, II, V, VII and X, possibly explaining the antinociceptive effects against abdominal pain in IBS (Sinniger et al., ). With the addition of a H 2 S‐releasing moiety to trimebutine, additional effects and mechanisms of action are to be expected with the GIC‐1001 compound.…”

A Systematic Review of the Evidence for Central Nervous System Plasticity in Animal Models of Inflammatory-mediated Gastrointestinal Pain

“…It has been suggested that remodelling of CNS nociceptive networks is largely responsible [84][85][86] though until recently, this has been relatively unexplored in models of visceral inflammation. Immunohistochemistry (IHC) has been employed to investigate the properties of spinal cord and brainstem neurons during and after visceral inflammation 29,[33][34][35]45,46,48,63,64,68,75,77,79,80,[86][87][88][89][90][91][92][93][94][95][96][97] . This approach is based on the premise that structural remodeling of neural networks in the CNS underlies the exaggerated reflex behaviors observed after visceral inflammation [84][85][86] .…”

“…Most used c-Fos (20%), and expression of either marker was consistently increased 29,[33][34][35]45,63,64,68,80,[86][87][88]90,[92][93][94]96,97 . Neural activation was maximal in spinal cord segments T13-L1 and L6-S2 in models of colitis [33][34][35]45,48,63,86,87,93,94,96,97 , T3-L1 in pancreatitis 64,68,80,88,90,92 and T6 for gallbladder inflammation 29 . Labeling was observed in lamina I-VII and/or X, reflecting the diffuse termination of visceral afferents in the spinal cord compared to their cutaneous counterparts 29,[33][34][35]45,63,64,68,80,[86][87]…”

The small molecule mimetic agonist trimebutine of adhesion molecule L1 contributes to functional recovery after spinal cord injury in mice

“…The muscarinic acetylcholine receptor plays a crucial role in afferent bladder activation that enhances detrusor overactivity in spinal cord-injured rats ( Matsumoto et al, 2012 ), but this effect does not influence regeneration after spinal cord injury, so it is unlikely to be relevant for the observations in the present study. The trimebutine metabolite nor-trimebutine was shown to decrease Fos activation in the spinal cord and the sacral parasympathetic nucleus after chronic inflammation and this effect was suggested to underlie the decrease of abdominal contractions and abdominal pain after trimebutine treatment ( Sinniger et al, 2005 ). However, it was also suggested that activation and upregulation of Fos might be necessary for regeneration after SCI ( Sabin et al, 2015 ).…”