[Therapeutic targets].
Based on better recent knowledge of the factors involved in triggering visceral hyperalgesia, the therapeutic approach to irritable bowel syndrome (IBS) treatment is changing. The classical approach targeting first bowel movement alterations or motility disorders using spasmolytic agents has to be replaced by visceral antinociceptive drugs. Several mediators and receptors involved in gut hyperalgesia have already been identified. Serotonin (5-HT), tachykinins, CCK, NGF, and other mediators are involved in experimental models of gut hyperalgesia, and related receptor antagonists have already been introduced in clinical trials. However, IBS is associated with mucosal immune stimulation, considered a microinflammatory state associated with increased density of immunocytes and mast cells, offering new targets. Altered mucosal barrier permeability with increased entry of toxins and bacteria is considered to be responsible for the mucosal microinflammation. Endogenous but predominantly luminal factors have been identified as factors responsible for such altered permeability. These clinical data have opened the door to promising future drugs able to prevent or blunt such permeability alteration, which therefore may constitute a pathophysiological treatment for IBS.
Bueno
L
L
Unité de Neurogastroenterologie et Nutrition, 180 Chemin de Tournefeuille-BP3, 31931 Toulouse, France. lbueno@toulouse.inra.fr
D000818:Animals; D002766:Cholecystokinin / Q000037:antagonists & inhibitors; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000188:drug therapy*; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors; D009414:Nerve Growth Factors / Q000627:therapeutic use; D010276:Parasympatholytics / Q000627:therapeutic use; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000037:antagonists & inhibitors; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use; D012702:Serotonin Antagonists / Q000627:therapeutic use; D017366:Serotonin Receptor Agonists / Q000627:therapeutic use
D009414:Nerve Growth Factors; D010276:Parasympatholytics; D017473:Receptors, Opioid, kappa; D018039:Receptors, Tachykinin; D015842:Serine Proteinase Inhibitors; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D002766:Cholecystokinin; D009219:Myosin-Light-Chain Kinase