Study Of The Antinociceptive Effect Of Intrathecal AP5, A NMDA Receptor Antagonist, And Its Mechanism

Part I The antinociceptic effect of visceral intrathecal AP5 in ratsObjective To investigate the effect and relation of the intrathecal (i.t.) administration of AP5, a competitive NMDA receptor antagonist, on colorectal distention-induced responses of visceral noxious stimulus in rats. Methods To utilize colorectal distention-induced visceral noxious stimulus. The male SD rats were randomly divided into control group, AP5 1.5ug group, AP5 3μg group, AP5 6ug group, AP5 12ug group, AP5 24μg group(n=6), which were administrated intrathecally, to observe the effect of the pain threshold when Abdominal Withdrawal Reflex(AWR) achieve 3 grade. Results In AP5 3μg and more than 3ug groups, threshold of visceral pain was raised to 26.67±7.69, 29.83±10.36, 41.67±17.69 and 63.00±17.24mmHg respectively. There were significance difference compared with control group (p<0.05, p<0.01) . AP5 inhibited CRD-induced visceral noxious stimulus and its effects were dose-dependent and time-dependent. Conclusions Competitive NMDA receptor antagonist AP5 inhibit CRD-induced visceral noxious stimulations and with dose-effect relationship and time -effect relationship. Part II The visceral Antinociceptive Effect of intrathecal AP5 bynaloxone in rats.Objective To investigate the antinociceptive effect of intrathecal AP5 and it combinedwith intraperitoneal naloxone in rats. Methods To utilize colorectal distention-induced visceral noxious stimulus. The male SD rats were randomly divided into control group, AP5 groups (n=6) respectively The visceral antinociceptive effects were compared between intrathecal AP5 and that after intraperitoneal naloxone. Results The visceral antinociceptive effects were significantly depressed after intraperitoneal naloxone 0.5mg/kg.in every AP5 groups. The naloxone 0.5mg/kg was adminstrated intra-peritoneum befor the adminstration of AP5 3ug, AP5 6ug and AP5 12ug 10 min, and analgesia effect was antogonisted by naloxone partially. The pressure of colorectal distension was 23.33±4.84 mmHg in AP5 3ug and naloxone 0.5mg/kg groups and it was 35.83±10.38 mmHg in AP5 3ug group, it was 30.33±4.59mmHg in AP5 6ug and naloxone group and 39.83±12.48 mmHg in AP5 6ug group, and 37.83±15.99 mmHg in AP5 12ug and naloxone and 66.00± 19.02 mmHg in AP5 12ug group respectively. There were significance difference between AP5 and AP5 combined with naloxone group (p<0.05) . Conclusions Naloxone maybe partialy antagonism visceral antinociceptive effect of AP5 and opioid receptor may participate the action of AP5 on spinal cord in rats. Part III The Antinociceptive Effect of intrathecal AP5 was increased bymidazolam in rats.Objective To investigate the antinociceptive effect of intrathecal AP5 and it combined with intraperitoneal midazolam in rats. Methods To utilize colorectal distention-induced visceral noxious stimulus. The male SD rats were randomly divided into control group, AP5 groups (n=6) respectively The visceral antinociceptive effects were compared between intrathecal AP5 and that after intraperitoneal midazolam. Results The visceral antinociceptive effects were significantly increased after intraperitoneal midazolam lmg/kg.in every AP5 groups. Midazolam lmg/kg was adminstrated intra-peritoneum befor the adminstration of AP5 1.5ug, AP5 3ug and AP5 6ug 10 min. The analgesia effect was increased by midazolam .the pressure of colorectal distension was 45.33±20.54mmHg in AP5 1.5|xg and midazolam lmg/kg groups and it was 25.33±6.77 mmHg in AP5 1.5(j,g group, it was 58.33±18.44mmHg in AP5 3ug and midazolam lmg/kg group and 35.83±10.38 mmHg in AP5 3ug group and 69.00±12.70 mmHg in AP5 6ug and midazolam lmg/kg and 40.00±9.94 mmHg in AP5 6ug group respectively. There were significance difference between AP5 and AP5 combined with midazolam group (p<0.05). Conclusions The antinociceptive effect of intrathecal AP5 was increased by midazolam in rats.