Effects of laparotomy on spontaneous exploratory activity and conditioned of operant responding in the rat - A model for postoperative pain
Effects of laparotomy on spontaneous exploratory activity and conditioned of operant responding in the rat - A model for postoperative pain
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DOI：
10.1097/00000542-200407000-00030
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发表时间：
2004-07-01
期刊：
影响因子：
8.8
通讯作者：
Eisenach, JC
中科院分区：
文献类型：
--
作者：
Martin, TJ;Buechler, NL;Eisenach, JC
背景：手术后疼痛的治疗是止痛剂的主要应用，尤其是腹部手术后。镇痛药显示出一些有限的副作用，包括镇静、认知障碍和肠梗阻。虽然已经开发了几种术后啮齿动物模型，但这些模型并没有解决这些问题。方法：建立大鼠肋下切口穿透腹腔的模型。使用探索性运动活动和条件操作反应来评估这种手术的行为效果。在两种行为范式下评估吗啡和酮咯酸的作用。结果：手术后24小时，剖腹手术减少了大约50%的行走和饲养，刻板印象（小的受限运动）受到较小程度的影响。剖腹手术对条件操作反应的影响更为复杂。术后2 ~ 3天蔗糖粒总数减少；然而，所需的时间增加了2周。吗啡能逆转手术对行走和刻板印象的影响，但对饲养没有影响，5 mg/kg酮罗拉酸使吗啡的剂量效应曲线向左偏移。酮咯酸可显著改善剖腹手术后的手术反应，无效剂量的吗啡和酮咯酸联合使用可产生积极反应。结论：目前的模型与临床所见的术后疼痛行为方面是一致的。吗啡和酮咯酸单独或联合使用的效果与临床报道的镇痛效果和副作用的发生一致。
Background: Treatment of postsurgical pain is a major use of analgesics, particularly after abdominal surgery. Analgesics display a number of limiting side effects, including sedation, cognitive impairment, and ileus. Although several postoperative rodent models have been developed, these models do not address these concerns.Methods: A model is presented in the rat in which a subcostal incision is performed, penetrating into the peritoneal cavity. The behavioral effects of this surgical procedure are assessed using exploratory locomotor activity and conditioned operant responding. The effects of morphine and ketorolac were assessed in both behavioral paradigms.Results: Laparotomy decreased ambulation and rearing by approximately 50% 24 h after surgery, and stereotypy (small confined movements) was affected to a lesser degree. The effects of laparotomy on conditioned operant responding were more complex. Total number of sucrose pellets earned was decreased for 2-3 days after laparotomy; however, the amount of time required was increased for up to 2 weeks. Morphine reversed the effects of surgery on ambulation and stereotypy but not rearing, and the dose-effect curve for morphine was shifted to the left by 5 mg/kg ketorolac. Ketorolac produced significant improvement in operant responding after laparotomy, and coadministration of ineffective doses of morphine and ketorolac produced a positive response.Conclusion: The current model is consistent with behavioral aspects of postoperative pain seen clinically. The effects of morphine and ketorolac alone and in combination were consistent with the reported analgesic efficacy and occurrence of side effects found with these agents clinically.