Antinociceptive efficacy of lacosamide in rat models for tumor- and chemotherapy-induced cancer pain
Antinociceptive efficacy of lacosamide in rat models for tumor- and chemotherapy-induced cancer pain
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DOI：
10.1016/j.ejphar.2007.02.041
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发表时间：
2007-06-22
影响因子：
5
通讯作者：
Stoehr, Thomas
中科院分区：
文献类型：
--
作者：
Beyreuther, Bettina K.;Callizot, Noelle;Stoehr, Thomas
疼痛是癌症患者最常见的躯体症状，大多数患者存在不止一处疼痛部位。目前的治疗缺乏充分的疗效。基于该领域对新方法的需求，拉考沙胺（SPM 927，(R)-2 - 乙酰氨基 - N - 苄基 - 3 - 甲氧基丙酰胺，先前称为harkoseride或ADD 234037）是一系列专门作为抗惊厥药物候选物合成的功能化氨基酸中的一员，其全身给药的效果在大鼠肿瘤诱发的骨癌疼痛模型和化疗诱发的神经性疼痛模型中进行了研究。在将MRMT - 1细胞注射到胫骨诱发的大鼠骨癌疼痛模型中，拉考沙胺抑制触觉异常性疼痛（20、40 mg/kg，腹腔注射）、热痛觉过敏（30 mg/kg）并减少负重差异（40 mg/kg）。吗啡（5 mg/kg，皮下注射）能有效抑制触觉异常性疼痛和负重，但不能减轻热痛觉过敏。在长春新碱诱发的神经性疼痛模型中，拉考沙胺在10和30 mg/kg时减轻冷板（4℃）上的热异常性疼痛，在3 mg/kg时甚至能减轻温板（38℃）和热板（52℃）上的热异常性疼痛。拉考沙胺在10和30 mg/kg时抑制触觉异常性疼痛和机械性痛觉过敏。与拉考沙胺相反，吗啡（3 mg/kg，皮下注射）对机械性痛觉过敏没有作用。拉考沙胺在动物的骨癌疼痛模型以及化疗诱发的神经性疼痛模型中作为镇痛药是有效的，甚至在吗啡无效（3或5 mg/kg，皮下注射）的情况下也能减轻痛觉过敏。(c) 2007爱思唯尔公司。版权所有。
Pain is the most common physical symptom of cancer patients, with most patients experiencing more than one site of pain. Current treatments lack full efficacy. Based on the need for new approaches in that field the effect of systemic administration of lacosamide (SPM 927, (R)-2acetamido-N-benzyl-3-methoxypropionamide, previously referred to as harkoseride or ADD 234037), a member of a series of functionalized amino acids that were specifically synthesized as anticonvulsive drug candidates, was examined in rats in a tumor-induced bone cancer pain model and in a chemotherapy-induced neuropathic pain model. Lacosamide inhibited tactile allodynia (20, 40 mg/kg, i.p.), thermal hyperalgesia (30 mg/kg) and reduced weight-bearing differences (40 mg/kg) in the rat model of bone cancer pain induced by injection of MRMT-1 cells into the tibia. Morphine (5 mg/kg, s.c) was effective inhibiting tactile allodynia and weight bearing but could not reduce thermal hyperalgesia. In the vincristine-induced neuropathic pain model, lacosamide attenuated thermal allodynia, on the cold plate (4 degrees C), at 10 and 30 mg/kg, and in the warm (38 degrees C) and hot plate (52 degrees C) even at 3 mg/kg. Tactile allodynia and mechanical hyperalgesia were inhibited by lacosamide at 10 and 30 mg/kg. In contrast to lacosamide, morphine (3 mg/kg, s.c.) had no effect on mechanical hyperalgesia. Lacosamide is effective as an analgesic in a bone cancer pain model as well as chemotherapy-induced neuropathic pain model in animals and even reduced hyperalgesia where morphine did not (3 or 5 mg/kg, s.c.). (c) 2007 Elsevier B.V. All rights reserved.