胍丁胺对鞘内吗啡镇痛作用的影响

Effect of agmatine on intrathecal morphine analgesia

目的观察脊髓水平给予胍丁胺对鞘内吗啡镇痛耐受的影响。方法 (1)将24只SD大鼠分为4组:鞘内注射生理盐水(15μL)对照组,鞘内注射吗啡(15μg/15μL)组,鞘内给予胍丁胺(12.5μg/15μL)组,鞘内同时给予吗啡(15μg/5μL)+胍丁胺(12.5μg/10μL)组,每组6只。4组大鼠均于鞘内给药后5 min于跖部皮下注射0.2 mg蜜蜂毒致痛,观察并记录1 h内大鼠的自发缩足反射次数。(2)将24只SD大鼠分为3组:鞘内生理盐水(15μL)对照组,鞘内吗啡耐受组(每天2次鞘内注射吗啡15μg/5μL,连续4 d),鞘内吗啡耐受+胍丁胺组(每天2次鞘内注射吗啡15μg/5μL,连续4 d,第4天同时注射胍丁胺12.5μg/10μL),每组8只。其中半数大鼠于鞘内给药后检测热刺激潜伏期和机械刺激阈值,另半数大鼠于最后一次给药后10 min经足底皮下注射0.2 mg蜜蜂毒致痛,观察并记录1 h内大鼠的自发缩足反射次数。结果 (1)与对照组比较,鞘内吗啡和胍丁胺联合用药组蜜蜂毒诱致大鼠自发缩足反射次数明显减少(P<0.05)。(2)在吗啡耐受模型上,胍丁胺+吗啡联合用药组与生理盐水对照组比较,可显著提高大鼠热刺激潜伏期和机械刺激阈值(P<0.05);同样,胍丁胺+吗啡联合用药组对蜜蜂毒诱致自发痛的抑制作用也显著强于吗啡耐受组,1 h内大鼠自发缩足反射次数明显减少(P<0.05)。结论鞘内胍丁胺对吗啡镇痛具有协同作用,同时也可翻转鞘内重复注射吗啡所引起的耐受。

Objective To observe the effect of intrathecal agmatine（AG） at the spinal cord level on morphine tolerance. Methods （1） Twenty-four SD rats were divided into four groups： control group, pure intrathecal injection（i, t. ） of saline （15μL） ; morphine group, i.t. morphine（15 μg/15 μL） ; AG group, i.t. AG （12.5 μg/15μL） ; and morphine＋AG group, i.＇t. morphine （15 μg/5 μg ） and AG （12. 5 μg/10 μL）. Rats of the four groups were injected with 0. 2 mg bee venom subcutaneously in the plantar 5 min after i. t, and the numbers of spontaneous paw withdrawal reflex were recorded within 1 hour. （2） Twenty-four SD rats were divided into three groups： control group, pure intrathecal saline（15μL）; morphine tolerance group, i.t. morphine（15 μg/5 μL） twice a day for 4 consecutive daysl and morphine tolerance＋AG group, i. t. morphine（15 μg/5 μL）twice a day for 4 consecutive days, on the fourth day the rats also received AG（12.5μg/10 μL）. Half of the rats were examined for thermal paw withdrawal latency and mechanical withdrawal threshold after i. t, and the other half was injected with 0. 2 mg bee venom subcutaneously in the plantar 10 min after last dose; the number of spontaneous paw withdrawal reflex were recorded within 1 hour. Results （1） Compared with the control group, the numbers of flinches of intrathecal morphine and AG groups were significantly reduced（P〈0.05） . （2） In intrathecal morphine tolerance model, the thermal paw withdrawal latency and mechanical withdrawal threshold were significantly increased in the morphine tolerance＋AG group compared with the control group （P〈0.05） ; morphine tolerance ＋ AG group had significantly stronger inhibitory effect against spontaneous s.c. BV-induced pain, with the number of spontaneous flinches within 1 hour decreased significantly in the morphine tolerance ＋ AG group（P〈0. 05）. Conclusion Intrathecal AG has synergistic effect with morphine in pain relieving, and it can also reverse the morphine tolerance induced by repeated i.t. injection.