Jin Hee Cheol, Keller Amber J, Jung Jong Kwon, Subieta Alberto, Brennan Timothy J
Department of Anesthesia, University of Iowa College of Medicine, Iowa City, IA 52242-1079, USA.
Anesth Analg. 2007 Oct;105(4):1152-9, table of contents. doi: 10.1213/01.ane.0000281435.58012.e3.
We evaluated the epidural administration of tezampanel, a non-N-methyl-d-aspartate receptor antagonist, in a rat model for postoperative pain. We sought to determine if this drug affects nociception when administered epidurally by testing its effects on responses to heat in normal rats. The effects of epidural tezampanel on pain-related behaviors in rats that underwent plantar incision were also studied.
Rats were anesthetized and epidural catheters were placed. One day after epidural catheterization, the baseline heat withdrawal latency was measured. Epidural tezampanel or morphine was tested for analgesia by examining their effects against heat withdrawal latency. Motor function was also tested. Comparisons to subcutaneous drug administration were made. Other rats underwent plantar incision after epidural catheterization to assess pain behavior caused by incision. The effects of epidural tezampanel on the cumulative pain scoring, based on guarding, the withdrawal threshold to von Frey filament application, and the withdrawal latency to heat, were measured. The effects of epidural tezampanel on arterial blood pressure and heart rate were also tested.
Both epidural morphine and epidural tezampanel increased withdrawal latency to heat. Only subcutaneous morphine affected heat withdrawal latency. After plantar incision, epidural tezampanel decreased the median guarding pain score, increased the heat withdrawal latency and increased the mechanical withdrawal threshold indicating analgesic effects. Arterial blood pressure and heart rate did not change after epidural drug administration.
These experiments demonstrate that epidural administration of tezampanel produces analgesia to heat, motor side effects in some rats, and reduces pain behaviors caused by incision. No systemic analgesia was apparent using the largest dose.
我们在大鼠术后疼痛模型中评估了非 N-甲基-D-天冬氨酸受体拮抗剂替扎帕奈的硬膜外给药情况。我们试图通过测试其对正常大鼠热反应的影响来确定该药物硬膜外给药时是否影响痛觉感受。还研究了硬膜外给予替扎帕奈对足底切开大鼠疼痛相关行为的影响。
将大鼠麻醉并放置硬膜外导管。硬膜外导管置入一天后，测量基线热缩足潜伏期。通过检查硬膜外给予替扎帕奈或吗啡对热缩足潜伏期的影响来测试其镇痛效果。还测试了运动功能。与皮下给药进行了比较。其他大鼠在硬膜外导管置入后进行足底切开，以评估切开引起的疼痛行为。测量硬膜外给予替扎帕奈对基于警戒的累积疼痛评分、对冯弗雷细丝施加的撤针阈值以及对热的撤针潜伏期的影响。还测试了硬膜外给予替扎帕奈对动脉血压和心率的影响。
硬膜外给予吗啡和替扎帕奈均增加了热缩足潜伏期。只有皮下给予吗啡影响热缩足潜伏期。足底切开后，硬膜外给予替扎帕奈降低了中位警戒疼痛评分，增加了热缩足潜伏期并提高了机械撤针阈值，表明具有镇痛作用。硬膜外给药后动脉血压和心率未发生变化。
这些实验表明，硬膜外给予替扎帕奈可产生对热的镇痛作用，在一些大鼠中产生运动副作用，并减少切开引起的疼痛行为。使用最大剂量时未观察到明显的全身镇痛作用。
