Prophylactic Use Of 5-HT₃ Receptor Antagonist To The Visceral Pain Hypersensitivity And The Colon Substance P Expression In Developing Rat

Prophylactic use of 5-HT3 receptor antagonist to the visceral pain hypersensitivity and the colon substance P expression in developing ratObjective To explore the effect of prophylactic use of 5-HT3 receptor antagonist to the visceral sensitivity and the colon substance P expression in detrimental colorectal irritation (CI) stimulation in neonatal period on developing rat by the method of behavior and electrophysiology research. Compare with the colon substance P expression in different group. To explore the effort of abnormal expression of colon substance P expression in the formation of rats'visceral pain hypersensitivity. This study can provide the theoretical basis for taking the preventive measures and the development of therapeutic drugs in clinic.Method①32 neonatal rats were divided into four groups by 2×2 factorial design with each 8. Group A1B1 imposed on CI at neonatal period and imposed on ramosetron intraperitoneal injection in 15～21day; Group A1B2:imposed on CI at neonatal period and not imposed on ramosetron intraperitoneal injection in 15～21day; Group A2B1:not imposed on CI at neonatal period and imposed on ramosetron intraperitoneal injection in 15～21day; Group A2B2: not imposed on CI at neonatal period and not imposed on ramosetron intraperitoneal injection in 15～21day. Then, conventionally breeding till the young period (6-week age), the following study was implemented:by the method of abdonminal withdrawal reflex (AWR),pain thresholds and electrophysiological study on external oblique to evaluate visceral algesthesia of intestinal tract. To select descending colon to do patholigical examination.②32 neonatal rats were divided into four groups by 2×2 factorial design with each 8. Group A1B1 imposed on CI at neonatal period and imposed on ramosetron intraperitoneal injection in 15～21day; Group A1B2:imposed on CI at neonatal period and not imposed on ramosetron intraperitoneal injection in 15～21day; Group A2B1:not imposed on CI at neonatal period and imposed on ramosetron intraperitoneal injection in 15～21day; Group A2B2: not imposed on CI at neonatal period and not imposed on ramosetron intraperitoneal injection in 15～21day. Then, conventionally breeding till the young period (6-week age), colons were analyzed through immunohisrochemical coloration and computer image analyzing system. SPSS 13.0 software for Windows was used in all statistical tests. The value ofα=0.05 was considered significant.Result①When imposed on CI at neonatal period for building visceral hypersensitivity model,the pain thresholds were decreased at 6-week age. The AWR scores were increased. There were a significant main effect for AWR scores at different pressures (F=47.79,6.61,26. 30,4.84,all P < 0.05). Prophylactic use of 5-HT3 receptor antagonist ramosetron in developing rat ,the AWR scores were decreased. There were a significant main effect for AWR scores at different pressures(F=23.74,11.88,4.74,4.20,4.76,all P<0.05). When imposed on CI at neonatal period, the amplitudes of spike EOMA were increased at different CRD pressures. There were a significant main effect for the amplitudes of spike EOMA at different pressures(F=9.00,6.50,8.99,4.02,.98,all P≤0.05).Four groups of rats did not any pathological lesion in descending colon.②At 6-week age,there were many immune positive brown-yellow granules in mucous layers,submucosa layers and muscular layers of group A1B2.There are farthing immune positive brown-yellow granules in mucous layers,submucosa layers and muscular layers of group A1B1,. In group A1B1,integral optical density values of substance p were significantly higher in muscular layers than mucous and submucosa layers.In group A1B2 ,group A2B1 and group A2B2,integral optical density values of substance p were no significantly different among different layers. Furthermore take random analysis of main effect value for integral optical density values of substance p in different colon layers.The main effect is imposed on CI at neonatal period and prophylactic use of ramosetron. They were significantly different between mucous layers and muscular layers(P=0.002).And they were significantly different between submucosa layers and muscular layers(P=0.004).They were no significantly different between mucous layers and submucosa layers(P=0.139). Integral optical density values of substance p were effected by CI at neonatal period and prophylactic use of 5-HT3 receptor antagonist ramosetron in developing rat. By CI at neonatal period, the SP immunohistochemistry integral optical density values of different colon layers were increased. Integral optical density values were increased more significantly in mucous and submucosa layers than muscular layers. Prophylactic use of ramosetron, different colon layers of SP integral optical density values were decreased.Conclusion①The persistent CI in neonatal period can result in low pain threshold and chronic visceral hypersensitivity in developing rats, histological change was not found in colorectal tissue. Prophylactic use of 5-HT3 receptor antagonist can decrease visceral hypersensitivity in developing rat.②The occurrence mechanism of visceral pain hypersensitivity in this model may be related to the increase expression of SP.