Effect Of Spinal NMDA Receptors On Chronic Visceral Hypersensitivity In Rats

Objective1.To establish a model of chronic visceral hypersensitivity2. To study the relationship of between spinal NMDA receptors and chronic visceral hypersensitivity in rats.MethodsSprague-Dawley(SD)rats are used as study subject. The model of visceral hypersensitivity was established by colorectal distensions (CRD) on neonatal rats 8-15 days after their birth. Two months later, Screening hypersensitive rats by abdominal withdrawal reflex(AWR).The hypersensitive rats were divided into two groups, MK-801 was given by intrathecal administration in one group and artificial cerebrospinal fluid (ASCF)was given by intrathecal administration in another group, the same done in control rats. Responses to CRD were compared by the spike of External oblique of abdomen (EOOA)between model and control rats by intrathecal administration of NMDA receptor antagonist MK-801 and ACSF.The changes in NR2B protein expression in the spinal cord was detected by immuno-histochemical techniquesResults1. Ways of evaluation of Model①evaluating visceral hypersensitivity by the scores of AWR The scores of AWR in model rats were significantly higher than those in control rats at 20～60mmHg CRD(P<0.05), but no significant difference at 80 mmHg.The Pain threshold was 30.418±1.34 mmHg in control rats and 13.125±1.34 mmHg in model rats(P<0.001).②evaluating visceral hypersensitivity by the spikes of EOOA The spikes of EOOA in model rats were significantly higher than those in control rats at 20～60mmHg CRD(P<0.05),while no significant difference at 80 mmHg.The Pain threshold is 37.5±4.53 mmHg in control rats and 25.0±3.27 mmHg in model rats(P<0.05).2. The spike of EOOA significantly reduced and the pain threshold significantly increased after intrathecally administration of MK-801 (1.5nmol/10μl)in model rats(P<0.05), while there were no significant differences in control rats between before and after intrathecally administration of MK-801 (1.5nmol/10μl).3. The NR2B protein were expressed in every laminae of the spinal dorsal horn of T12-L1,L6-S2 segment in model and control group. Most of positive cells were round or elliptical neurons, and the cytoplasm was stained as brown. The optical density is significantly higher in model+ASCF group than those in the other groups(P<0.01);it was significantly reduced after intrathecally administration of MK-801 (1.5nmol/10μl)in model group (P<0.05) .Conclusion1. There are visceral hypersensitivity in model rats and no pathological change in colon.2. AWR and the spikes of EOOA can be used to assess a model of chronic visceral hypersensitivity.3. Chronic visceral hypersensitivity in rats could be associated with spinal NMDA receptors.