Efficacy of duloxetine, a potent and balanced serotonergic and noradrenergic reuptake inhibitor, in inflammatory and acute pain models in rodents
Efficacy of duloxetine, a potent and balanced serotonergic and noradrenergic reuptake inhibitor, in inflammatory and acute pain models in rodents
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DOI：
10.1124/jpet.104.075960
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发表时间：
2005-02-01
影响因子：
3.5
通讯作者：
Shannon, HE
中科院分区：
文献类型：
--
作者：
Jones, CK;Peters, SC;Shannon, HE
在小鼠甩尾和热板急性伤害性疼痛模型、小鼠醋酸诱导扭体、大鼠角叉菜胶诱导热痛觉过敏和机械性异常性疼痛以及大鼠辣椒素诱导机械性异常性疼痛的持续性和/或炎性疼痛模型中，评价了度洛沙汀（一种选择性但平衡的肾上腺素能和去甲肾上腺素能再摄取抑制剂）。在急性疼痛模型中，度洛沙汀对小鼠甩尾试验中的反应潜伏期无显著影响，但在小鼠热板试验中使反应潜伏期适度增加。吗啡在小鼠甩尾和热板试验中均产生剂量相关的镇痛作用。在炎性和/或持续性疼痛模型中，度洛沙汀、吗啡和布洛芬使醋酸诱导的小鼠扭体反应呈剂量相关性降低。度洛沙坦、布洛芬和加巴喷丁也能剂量依赖性逆转大鼠角叉菜胶引起的热痛觉过敏和机械性异常性疼痛。此外，度洛沙汀和吗啡均显著降低了大鼠中辣椒素诱导的机械性异常性疼痛。度洛西汀和加巴喷丁对小鼠的Rotorod试验没有实质性影响，而吗啡和布洛芬产生了显著的损害。我们的数据表明，在对急性伤害感受或运动表现有中度影响或无影响的剂量下，度洛沙坦可能有效治疗持续性和/或炎性疼痛状态。
Duloxetine, a selective but balanced serotonergic and noradrenergic reuptake inhibitor, was evaluated in the acute nociceptive pain models of tail flick and hot plate in mice and in the persistent and/or inflammatory pain models of acetic acid-induced writhing in mice, carrageenan-induced thermal hyperalgesia and mechanical allodynia in rats, and capsaicin-induced mechanical allodynia in rats. In acute pain models, duloxetine had no significant effect on response latency in the mouse tail-flick test but produced modest increases in response latencies in the mouse hot plate test. Morphine produced dose-related analgesic effects in both the mouse tail-flick and hot plate tests. In models of inflammatory and/or persistent pain, duloxetine, morphine, and ibuprofen produced dose-related decreases in acetic acid-induced writhing in mice. Duloxetine, ibuprofen, and gabapentin also produced dose-dependent reversals of both thermal hyperalgesia and mechanical allodynia produced by carrageenan in rats. In addition, both duloxetine and morphine produced a significant reduction of capsaicin-induced mechanical allodynia in rats. Duloxetine and gabapentin were without substantial effect on the Rotorod test in mice, whereas morphine and ibuprofen produced a significant impairment. Our data indicate that duloxetine may be efficacious in the treatment of persistent and/or inflammatory pain states at doses that have modest or no effect on acute nociception or motor performance.