Neuroscience Research Center and Department of Pharmacology, Shahid Beheshti University of Medical Sciences, Tehran, Islamic Republic of Iran.
Eur J Pharmacol. 2012 Jan 15;674(2-3):332-6. doi: 10.1016/j.ejphar.2011.10.026. Epub 2011 Oct 26.
Postoperative pain and its control remain one of the most important issues in the field of surgery and health care systems. Morphine is a potent and effective analgesic, but substance abuse patients can manifest cross-tolerance to it, making it difficult to satisfy their analgesic/anesthetic requirements. As carbamazepine has shown antinociceptive properties in a variety of experimental and clinical settings, in the present study, we evaluated its potential antiallodynic effects on postoperative pain in naïve and morphine-dependent rats. Male rats were assigned to morphine-dependent and naïve groups and received intraperitoneally drug vehicles as control group, 3mg/kg morphine, 5, 10 or 15 mg/kg carbamazepine or 5mg/kg carbamazepine plus 3mg/kg morphine as a combination therapy 2 and 24h after surgery. Morphine-dependency was induced with multiple doses of morphine administered i.p. and plantar incision was made on the hind paw to simulate the postoperative pain. Paw withdrawal threshold (PWT) was obtained by von Frey filaments every 30 min after drug injection for up to 180 min. Morphine at 3mg/kg exerted antiallodynic effects in naïve rats and a decreased antinociception was observed in morphine-dependent rats. In contrast, 5mg/kg carbamazepine did not significantly alter PWT in naives but it was effective in dependent rats. 10 and 15 mg/kg carbamazepine attenuated allodynia following surgery in both groups. Co-administration of 5mg/kg carbamazepine with 3mg/kg morphine produced higher analgesia in morphine-dependent incised rats and prolonged antinociception as compared to morphine alone (P<0.05). Thus carbamazepine may potentiate the analgesic effect of chronically administered morphine on postoperative pain model in morphine-dependent rats.
术后疼痛及其控制仍然是外科和医疗保健系统领域最重要的问题之一。吗啡是一种有效而有效的镇痛药，但药物滥用患者可能表现出对其的交叉耐受，使其难以满足他们的镇痛/麻醉要求。由于卡马西平在各种实验和临床环境中显示出镇痛作用，在本研究中，我们评估了其对术后疼痛的潜在抗伤害感受作用在天真和吗啡依赖的大鼠中。雄性大鼠被分为吗啡依赖和天真组，并接受腹腔内药物载体作为对照组，3mg/kg 吗啡，5、10 或 15mg/kg 卡马西平或 5mg/kg 卡马西平加 3mg/kg 吗啡作为组合治疗，手术后 2 和 24 小时。通过腹腔内给予多次吗啡剂量诱导吗啡依赖性，在后爪上进行足底切口以模拟术后疼痛。通过冯弗雷丝纤维在药物注射后每 30 分钟获得一次足底撤回阈值（PWT），最长可达 180 分钟。3mg/kg 吗啡对天真大鼠具有抗伤害感受作用，而在吗啡依赖大鼠中观察到镇痛作用减弱。相比之下，5mg/kg 卡马西平在天真大鼠中对 PWT 没有显著影响，但在依赖大鼠中有效。10 和 15mg/kg 卡马西平减轻了两组手术后的伤害感受。与单独使用吗啡相比，5mg/kg 卡马西平与 3mg/kg 吗啡联合给药在吗啡依赖切开大鼠中产生更高的镇痛作用，并延长了镇痛作用（P<0.05）。因此，卡马西平可能增强慢性给予吗啡对吗啡依赖大鼠术后疼痛模型的镇痛作用。
