Effect Of Ionotropic Glutamate Receptor On Visceral Hypersensitivity Induced By Inflammatory

Objective:Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorders (FGIDs). The pathophysiology underlying IBS remains elusive. However, visceral hypersensitivity (VH) is currently the leading hypothesis to explain painful symptoms experienced by IBS patients. As many as 26% of patients suffered from acute gastroenteritis that resolved before developing IBS. The onset of IBS with the appearance of VH following infection has now been recognized. Post-infection VH may partially result from the sensitization of primary afferent fibers innervating the gastrointestinal tract, while central neuroplastic changes also contributes to its development. N-methyl-D-aspartate (NMDA), a-amino-3-hydroxy-5-methylisoxazolone-4-propionic acid (AMPA), and kainate (KA) receptors are members of the ionotropic glutamate receptor (iGluR) family and these receptors contribute to inflammatory pain, nociception and hyperalgesia. In this study, we have examined whether there are some changes of ionotropic glutamate receptors (iGluRs), including NR2A and NR2B (the subunits of NMDA receptor), GluR2 (the subunit of AMPA receptor) in anterior cingulate cortex (ACC) in post-inflammatory viscerally hypersensitive rats.Methods:Experiments were performed on adult male Sprague-Dawley rats (250-300g). Rats were randomly divided into two groups:VH group and control group. Deoxycholic acid was instilled into the rat colon to establish post-inflammatory VH rat model, rats in the control group received saline instead of DCA. The magnitude of visceromotor response (VMR) during colorectal distention (CRD) was used to measure the changes of viscerally hypersensitivity. Three weeks after DCA or saline injection, rats were used for studying visceral sensitivity, immunohistochemistry and western blot.Results:Deoxycholic acid significantly increased colorectal sensitivity to colorectal distention, the magnitude of VMR (60 mmHg) was higher in VH group compared to control rats (P< 0.05), the magnitude of VMR (30 mmHg) was slightly higher in VH group compared to control rats (P> 0.05). Immunohistochemistry indicated that the expression of NR2A, NR2B and GluR2 were all significantly increased in ACC of VH group compared with control (P< 0.05). Western blot also suggested the quantity of the NR2A, NR2B and GluR2 protein all up-regulated in ACC of VH rats compared with controls (P< 0.05).Conclusion:In the DCA induced VH rats, the NR2A, NR2B and GluR2 is all up-regulated in ACC, which means iGluRs might play an role in modulation of post-inflammatory visceral hypersensitivity.