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Abstract：
BACKGROUND: The present study aimed to compare the effects of the combined administration of two adjuvants, dopamine and phenylephrine, on the cutaneous analgesic effect and duration of mexiletine in rats.
METHODS: Nociceptive blockage was evaluated by the inhibition of response to skin pinpricks in rats via the cutaneous trunci muscle reflex (CTMR). After subcutaneous injection, the analgesic activities of mexiletine in the absence and presence of either dopamine or phenylephrine were assessed. Each injection was standardized into 0.6 ml with a mixture of drugs and saline.
RESULTS: Subcutaneous injections of mexiletine successfully induced dose-dependent cutaneous analgesia in rats. The results revealed that rats injected with 1.8 μmol mexiletine exhibited 43.75% blockage (%MPE), while rats injected with 6.0 μmol mexiletine showed 100% blockage. Co-application of mexiletine (1.8 or 6.0 μmol) with dopamine (0.06, 0.60, or 6.00 μmol) elicited full sensory block (%MPE). Sensory blockage ranged from 81.25% to 95.83% in rats injected with mexiletine (1.8 μmol) and phenylephrine (0.0059 or 0.0295 μmol), and complete subcutaneous analgesia was observed in rats injected with mexiletine (1.8 μmol) and a higher concentration of phenylephrine (0.1473 μmol). Furthermore, mexiletine at 6.0 μmol completely blocked nociception when combined with any concentration of phenylephrine, while 0.1473 μmol phenylephrine alone exhibited 35.417% subcutaneous analgesia. The combined application of dopamine (0.06/0.6/6 μmol) and mexiletine (1.8/6 μmol) resulted in increased %MPE, complete block time, full recovery time, and AUCs compared to the combined application of phenylephrine (0.0059 and 0.1473 μmol) and mexiletine (1.8/6 μmol) (p < 0.001).
CONCLUSIONS: Dopamine is superior to phenylephrine in improving sensory blockage and enhancing the duration of nociceptive blockage by mexiletine.
METHODS: Nociceptive blockage was evaluated by the inhibition of response to skin pinpricks in rats via the cutaneous trunci muscle reflex (CTMR). After subcutaneous injection, the analgesic activities of mexiletine in the absence and presence of either dopamine or phenylephrine were assessed. Each injection was standardized into 0.6 ml with a mixture of drugs and saline.
RESULTS: Subcutaneous injections of mexiletine successfully induced dose-dependent cutaneous analgesia in rats. The results revealed that rats injected with 1.8 μmol mexiletine exhibited 43.75% blockage (%MPE), while rats injected with 6.0 μmol mexiletine showed 100% blockage. Co-application of mexiletine (1.8 or 6.0 μmol) with dopamine (0.06, 0.60, or 6.00 μmol) elicited full sensory block (%MPE). Sensory blockage ranged from 81.25% to 95.83% in rats injected with mexiletine (1.8 μmol) and phenylephrine (0.0059 or 0.0295 μmol), and complete subcutaneous analgesia was observed in rats injected with mexiletine (1.8 μmol) and a higher concentration of phenylephrine (0.1473 μmol). Furthermore, mexiletine at 6.0 μmol completely blocked nociception when combined with any concentration of phenylephrine, while 0.1473 μmol phenylephrine alone exhibited 35.417% subcutaneous analgesia. The combined application of dopamine (0.06/0.6/6 μmol) and mexiletine (1.8/6 μmol) resulted in increased %MPE, complete block time, full recovery time, and AUCs compared to the combined application of phenylephrine (0.0059 and 0.1473 μmol) and mexiletine (1.8/6 μmol) (p < 0.001).
CONCLUSIONS: Dopamine is superior to phenylephrine in improving sensory blockage and enhancing the duration of nociceptive blockage by mexiletine.
摘要：
背景：本研究旨在比较两种佐剂联合给药的效果，多巴胺和去氧肾上腺素,美西律对大鼠皮肤镇痛作用及持续时间的影响。
方法：通过皮肤干肌肉反射（CTMR）抑制大鼠对皮肤针刺的反应来评估伤害性阻断。皮下注射后,评估了在不存在和存在多巴胺或去氧肾上腺素的情况下美西律的镇痛活性.每次注射用药物和盐水的混合物标准化为0.6ml。
结果：皮下注射美西律成功诱导大鼠剂量依赖性皮肤镇痛。结果显示，注射1.8μmol美西律的大鼠表现出43.75％的阻滞（％MPE），而注射6.0μmol美西律的大鼠显示100%阻断。美西律（1.8或6.0μmol）与多巴胺（0.06、0.60或6.00μmol）的共同施用会引起完全的感觉阻滞（％MPE）。在注射美西律(1.8μmol)和去氧肾上腺素(0.0059或0.0295μmol)的大鼠中,感觉阻滞范围为81.25%至95.83%,在注射美西律（1.8μmol）和较高浓度的去氧肾上腺素（0.1473μmol）的大鼠中观察到完全的皮下镇痛。此外，当与任何浓度的去氧肾上腺素联合使用时，6.0μmol的美西律完全阻断了伤害感受，而仅0.1473μmol去氧肾上腺素表现出35.417％的皮下镇痛。多巴胺(0.06/0.6/6μmol)和美西律(1.8/6μmol)联合应用导致%MPE增加,完整的块时间，完全恢复时间，和AUCs与去氧肾上腺素(0.0059和0.1473μmol)和美西律(1.8/6μmol)的联合应用相比(p<0.001)。
结论：多巴胺在改善美西律的感觉阻滞和延长伤害性阻滞的持续时间方面优于去氧肾上腺素。
方法：通过皮肤干肌肉反射（CTMR）抑制大鼠对皮肤针刺的反应来评估伤害性阻断。皮下注射后,评估了在不存在和存在多巴胺或去氧肾上腺素的情况下美西律的镇痛活性.每次注射用药物和盐水的混合物标准化为0.6ml。
结果：皮下注射美西律成功诱导大鼠剂量依赖性皮肤镇痛。结果显示，注射1.8μmol美西律的大鼠表现出43.75％的阻滞（％MPE），而注射6.0μmol美西律的大鼠显示100%阻断。美西律（1.8或6.0μmol）与多巴胺（0.06、0.60或6.00μmol）的共同施用会引起完全的感觉阻滞（％MPE）。在注射美西律(1.8μmol)和去氧肾上腺素(0.0059或0.0295μmol)的大鼠中,感觉阻滞范围为81.25%至95.83%,在注射美西律（1.8μmol）和较高浓度的去氧肾上腺素（0.1473μmol）的大鼠中观察到完全的皮下镇痛。此外，当与任何浓度的去氧肾上腺素联合使用时，6.0μmol的美西律完全阻断了伤害感受，而仅0.1473μmol去氧肾上腺素表现出35.417％的皮下镇痛。多巴胺(0.06/0.6/6μmol)和美西律(1.8/6μmol)联合应用导致%MPE增加,完整的块时间，完全恢复时间，和AUCs与去氧肾上腺素(0.0059和0.1473μmol)和美西律(1.8/6μmol)的联合应用相比(p<0.001)。
结论：多巴胺在改善美西律的感觉阻滞和延长伤害性阻滞的持续时间方面优于去氧肾上腺素。
