Antinociceptive effect in mice of intraperitoneal N-methyl-D-aspartate receptor antagonists in the formalin test
Antinociceptive effect in mice of intraperitoneal N-methyl-D-aspartate receptor antagonists in the formalin test
复制标题
DOI：
10.1016/s1090-3801(02)00086-1
复制
发表时间：
2003-01-01
影响因子：
3.6
通讯作者：
Rossi, F
中科院分区：
文献类型：
--
作者：
Berrino, L;Oliva, P;Rossi, F
虽然在福尔马林试验中，NMDA拮抗剂的抗伤害性作用得到了很好的认可，但这些化合物可能会引起不良的运动效应。这项研究的目的是确定NMDA拮抗剂的全身剂量，以诱导止痛而不引起副作用。雄性瑞士小鼠(30-40g)在右后爪背部皮下注射1.25%福尔马林(50mul)，并在福尔马林前或福尔马林后15min ip注射下列N-甲基-D-天冬氨酸受体拮抗剂之一：MK801(0.01、0.025和0.05 mg/kg)、美金刚(0.025、0.1和1 mg/kg)、氯胺酮(0.125、0.25和0.5 mg/kg)、右美沙芬(5、10和20 mg/kg)和CGP 801(4、4、4、4、4、4、4、4、4、4、4、4、4、4、4、4、4、4、4、4、4、4、4、4、4、4、4、4、4、4、4、4、4、4、4、4、4、4、4、4、4、4、4、4、4、4、4、4、5、4、4、4、4、4、4、4、4、5、4、4、4、4、4、4、4、4、4、5、10、10、6和8 mg/kg)。每隔5分钟记录一次与疼痛相关的行为(舔、抬、偏爱、抖动和退缩被治疗的爪子)，持续60分钟。在福尔马林实验的第二阶段(从第20分钟到第60分钟)，N-甲基-D-天冬氨酸受体拮抗剂与对照组相比，伤害性活性显著降低(P<；0.01)：在最高剂量下，MK801的伤害性活性为97.6+/-0.1%；美金刚为90.4+/-0.2%；氯胺酮为74.7+/-0.3%；右美沙芬为92.8+/-0.4%；CGP 37849为80.7+/-0.3%，而不影响协调性。NMDA拮抗剂的抗伤害效应强弱顺序为：MK 801>；美金刚>；氯胺酮>；右美沙芬；CGP37849。在福尔马林后给予NMDA拮抗剂(在止痛间隔期间)不影响福尔马林试验的后期。总而言之，全身应用NMDA受体拮抗剂可以减少福尔马林试验后期观察到的伤害性。(C)2002年国际疼痛研究协会欧洲分会联合会。爱思唯尔科学有限公司出版。版权所有。
Although the antinociceptive effect of NMDA antagonists in the formalin test is well recognised, these compounds can induce adverse motor effects. The aim of this study was to identify the systemic doses of NMDA antagonists that induce analgesia without causing side effects. Male Swiss mice (30-40 g) received a subcutaneous (sc) injection of 1.25% formalin (50 mul) in the dorsal surface of the right hind-paw and, 15 min before or after formalin, an ip injection of one of the following NMDA receptor antagonists: MK 801 (0.01, 0.025, and 0.05 mg/kg), memantine (0.1, 0.5, and 1 mg/kg), ketamine (0.125, 0.25, and 0.5 mg/kg), dextromethorphan (5, 10, and 20 mg/kg), and CGP 37849 (4, 6, and 8 mg/kg). Pain-related behaviour (licking, lifting, favouring, shaking, and flinching of the treated paw) was recorded at 5-min intervals for 60 min. The NMDA receptor antagonists significantly (p < 0.01) and dose-dependently reduced, versus controls, nociceptive activity during the second phase of the formalin test (from the 20th to the 60th min): at the highest doses, 97.6 +/- 0.1% with MK 801; 90.4 +/- 0.2% with memantine; 74.7 +/- 0.3% with ketamine; 92.8 +/- 0.4% with dextromethorphan; and 80.7 +/- 0.3% with CGP 37849, without affecting coordination. The rank order potency of antinociceptive activity of NMDA antagonists was: MK 801 > memantine > ketamine > dextromethorphan > CGP37849. The NMDA antagonists administered after formalin (during the analgesic interval) did not affect the late phase of the formalin test. In conclusion, systemic administration of NMDA receptor antagonists decreases the nociception observed during the late phase of the formalin test. (C) 2002 European Federation of Chapters of the International Association for the Study of Pain. Published by Elsevier Science Ltd. All rights reserved.