外周NMDA受体介导蜜蜂毒诱导的持续性伤害性反应的行为学研究(英文)

INVOLVEMENT OF PERIPHERAL NMDA RECEPTORS IN PERSISTENT NOCICEPTION INDUCED BY SUBCUTANEOUS BEE VENOM INJECTION: A BEHAVIORAL STUDY

为了探讨外周 NMDA受体是否介导大鼠足底皮下注入蜜蜂毒诱导的持续伤害性行为反应 ,本研究应用动物痛行为学定量方法评价局部用药对持续伤害性行为反应的作用效果。大鼠足底皮下注入蜜蜂毒可以诱导动物产生长达 1h以上的持续、单相性的自发痛反应 ,其表现为自发缩足反射、抬足、舔足甚至咬足行为。注入蜜蜂毒之前局部给予非竞争性的 NMDA受体通道阻断剂氯胺酮和 MK-80 1。局部注入 2 5 m mol/L和 5 0 mmol/L氯胺酮可剂量依赖性地抑制大鼠的缩足次数和抬足、舔足时间 ,其对缩足反射的抑制率分别为 2 0 .90± 2 .88%和 45 .76± 13 .99% ,对抬足、舔足时间的抑制率分别为 3 9.5 3± 10 .0 5 %和 5 9.94±5 .5 3 %。同样 ,局部注入 10 μmol/L和 10 0 μmol/L的 MK-80 1也产生了类似的抑制作用 ,其对缩足反射的抑制率分别为 2 2 .84±3 .12 %和 49.5 3± 5 .3 6% ;对抬足、舔足时间的抑制率分别为 17.49± 5 .67%和 5 3 .49± 3 .87%。然而 ,对侧足底注入氯胺酮和MK-80 1对同侧蜜蜂毒诱导的自发痛反应没有影响 ,说明氯胺酮和 MK-80 1的作用并非全身效应。本实验提示外周

The present study was to investigate whether peripheral NMDA receptors were involved in the persistent nociception induced by subcutaneous (s.c.) bee venom injection in the conscious rat by using quatitative pain scoring methods. s.c. bee venom injection into one hindpaw resulted in a persistent, monophasic nociceptive response characterized by continuously flinching, lifting and licking the injected paw for more than 1 h. The non competitive NMDA receptor channel blockers, ketamine and MK 801, were administered s.c. 5 or 20 min after bee venom. Local ketamine injection produced a suppression of flinching reflex by 20.90±2.88% and 45.76±13.99%, while that of lifting/licking time by 39.53±10.05% and 59.94±5.53%, at doses of 25 mmol/L and 50 mmol/L respectively without any motor disturbance. Local MK 801 resulted in an inhibition of flinching reflex by 22.84±3.12% and 49.53±5.36%, while that of lifting/licking time by 17.49±5.67% and 53.49±3.87%, at doses of 10 μmol/L and 100 μmol/L respectively also with no motor disturbance. However, s.c. administration of ketamine and MK 801 into a region symmetrical to the bee venom injection site on the contralateral hindpaw produced no change in the nociceptive behaviors, suggesting that the analgesic actions of ketamine and MK 801 were not the result of systemic effects. The present result suggests that peripheral NMDA receptors are involved in the production of persistent pain.