Pharmacology Department, Kerman University of Medical Sciences, 22 Bahman Blvd., Kerman, Iran.
Pharmacol Biochem Behav. 2013 Sep;110:249-54. doi: 10.1016/j.pbb.2013.07.021. Epub 2013 Aug 4.
Visceral pain currently represents one of the most important pain treatment challenges in clinical practice, and investigators across the world are continuously designing and conducting numerous studies in search of new analgesics and new combination therapies. The current study assessed the analgesic effects of saline, pregabalin (2, 5, 17, 50, 100, and 200 mg/kg, i.p.) and morphine (0.25, 0.5, 1, 3 and 5 mg/kg) alone or in combination on acetic-acid induced abdominal contractions in mice. The number of writhes and the inhibitory effects (as percentages, %E) were calculated as antinociception indexes. These indexes indicated that both pregabalin (Prg) and morphine (Mrp) produced dose-dependent antinociception. Pregabalin at 5 mg/kg (%E=32.5±4.0) or 2 mg/kg (%E=20.8±4.5) and morphine at 0.25 mg/kg (%E=20.2±7.8) and 0.5 mg/kg (%E=43.6±4.5) exhibited antinociceptive effects, and the combination of pregabalin and morphine produced significantly greater antinociceptive effects (%E=62.4±5.8 for Prg5+Mrp0.25; %E=71.7±4.8 for Prg5+Mrp0.5; and %E=54.1±4.0 for Prg2+Mrp0.25), although this enhancement was not observed when morphine was combined with 17 mg/kg pregabalin. Pre-treatment with 2 mg/kg (i.p.) naloxone did not affect increased analgesia when combined with these drugs. A dose-response curve was established for pregabalin at a fixed morphine dose and revealed that, at low doses, pregabalin dose-dependently enhanced the antinociceptive effects, while the opposite was true at high doses (17 and 25 mg/kg). In conclusion, pregabalin can produce levels of antinociception that are similar to those of morphine in acetic acid-induced viscero-somatic pain. The enhancement of antinociception produced by the co-administration of morphine and pregabalin is termed a supra-additive interaction and occurred at low doses but not at high doses. These findings militate for increased attention and caution in clinical settings.
内脏痛目前是临床实践中最重要的疼痛治疗挑战之一，全世界的研究人员一直在设计和进行大量研究，以寻找新的镇痛药和新的联合治疗方法。本研究评估了生理盐水、普瑞巴林（2、5、17、50、100 和 200mg/kg，ip）和吗啡（0.25、0.5、1、3 和 5mg/kg）单独或联合应用于乙酸诱导的小鼠腹部收缩的镇痛作用。扭体次数和抑制作用（以百分比表示，%E）被计算为镇痛指数。这些指数表明，普瑞巴林（Prg）和吗啡（Mrp）均产生剂量依赖性镇痛作用。普瑞巴林 5mg/kg（%E=32.5±4.0）或 2mg/kg（%E=20.8±4.5）和吗啡 0.25mg/kg（%E=20.2±7.8）和 0.5mg/kg（%E=43.6±4.5）表现出镇痛作用，普瑞巴林和吗啡联合使用产生了显著更大的镇痛作用（Prg5+Mrp0.25 为%E=62.4±5.8；Prg5+Mrp0.5 为%E=71.7±4.8；Prg2+Mrp0.25 为%E=54.1±4.0），尽管当吗啡与 17mg/kg 普瑞巴林联合使用时，并未观察到这种增强作用。预先给予 2mg/kg（ip）纳洛酮不会影响与这些药物联合使用时增加的镇痛作用。在固定吗啡剂量下建立了普瑞巴林的剂量反应曲线，结果表明，在低剂量时，普瑞巴林剂量依赖性地增强了镇痛作用，而在高剂量时则相反（17 和 25mg/kg）。总之，普瑞巴林在乙酸诱导的内脏躯体疼痛中可以产生与吗啡相似水平的镇痛作用。吗啡和普瑞巴林联合给药产生的镇痛增强作用称为超相加相互作用，仅在低剂量时发生，而在高剂量时不发生。这些发现提醒人们在临床环境中要更加关注和谨慎。
