Comparison of milnacipran, duloxetine and pregabalin in the formalin pain test and in a model of stress-induced ultrasonic vocalizations in rats
Comparison of milnacipran, duloxetine and pregabalin in the formalin pain test and in a model of stress-induced ultrasonic vocalizations in rats
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DOI：
10.1016/j.neures.2009.10.009
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发表时间：
2010-02-01
影响因子：
2.9
通讯作者：
Depoortere, R.
中科院分区：
文献类型：
--
作者：
Bardin, L.;Gregoire, S.;Depoortere, R.
5-羟色胺/去甲肾上腺素再摄取抑制剂米那普仑和度洛昔单抗以及α 2-δ 1钙通道阻滞剂普瑞巴林对纤维肌痛有效，纤维肌痛是一种以弥漫性慢性疼痛为特征并与应激相关的病症。我们比较了这些化合物（腹膜内途径），在大鼠模型的急性/炎症性疼痛（2.5%足底福尔马林）和应力诱导的超声发声（USV：22 kHz的电话后，介绍了条件刺激先前与足部电击）。在福尔马林试验中，米那普仑剂量依赖性地减弱爪抬高和舔体（最小有效剂量，MED：舔体/晚期2.5 mg/kg）。度洛沙汀的效力略高（MED = 0.63）。普瑞巴林还减少了舔爪/晚期（MED = 0.63），但高达160 mg/kg时，对爪子抬高（两个阶段）和舔爪（早期）无活性。米那普仑剂量依赖性地降低USV（MED = 10，20 mg/kg时几乎完全抑制）：度洛沙坦效力较低（MED = 20）。普瑞巴林（2.5-80 mg/kg）仅在40 mg/kg时具有显著活性。米那普仑、度洛沙坦和普瑞巴林在福尔马林试验中对舔爪/晚期（对应于具有中枢致敏成分的炎性疼痛）具有镇痛活性。在应激诱导的USV模型中，米那普仑是最有效的化合物。总之，福尔马林诱导的舔爪/晚期减少可能构成对炎性/中枢致敏疼痛的潜在活性的有用指标，如可能在纤维肌痛中表达的。(C)2009年爱思唯尔爱尔兰有限公司和日本神经科学学会。All rights reserved.
Milnacipran and duloxetine, serotonin/noradrenalin reuptake inhibitors, and pregabalin, a alpha(2)-delta(1) Ca2+ channel blocker, are efficacious against fibromyalgia, a condition characterized by diffuse chronic pain and associated with stress. We compared these compounds (i.p. route), in rat models of acute/inflammatory pain (2.5% intraplantar formalin) and stress-induced ultrasonic vocalization (USV: 22 kHz calls following presentation of a conditioned stimulus previously associated with foot-shocks). In the formalin test, milnacipran dose-dependently attenuated paw elevation and licking (minimal effective dose, MED: 2.5 mg/kg for licking/late phase). Duloxetine was slightly more potent (MED = 0.63). Pregabalin also reduced paw licking/late phase (MED = 0.63), but was inactive up to 160 mg/kg for paw elevation (both phases) and paw licking (early phase). Milnacipran dose-dependently reduced USV (MED = 10, near total inhibition at 20 mg/kg): duloxetine was less potent (MED = 20). Pregabalin (2.5-80 mg/kg) was only significantly active at 40 mg/kg. Milnacipran, duloxetine and pregabalin possess analgesic activity in the formalin test on paw licking/late phase (corresponding to inflammatory pain with a central sensitization component). In the stress-induced USV model, milnacipran was the most potent and efficacious compound. To summarize, reduction of formalin-induced paw licking/late phase might constitute a useful indicator of potential activity against inflammatory/centrally sensitized pain, as might be expressed in fibromyalgia. (C) 2009 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.