Synergistic analgesia of duloxetine and celecoxib in the mouse formalin test: a combination analysis.
Synergistic analgesia of duloxetine and celecoxib in the mouse formalin test: a combination analysis.
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小鼠福尔马林试验中度洛西汀和塞来考昔的协同镇痛作用：组合分析
DOI：
10.1371/journal.pone.0076603
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Wang W
中科院分区：
文献类型：
--
作者：
Sun YH;Dong YL;Wang YT;Zhao GL;Lu GJ;Yang J;Wu SX;Gu ZX;Wang W
度洛沙汀（一种5-羟色胺和去甲肾上腺素再摄取抑制剂）和塞来昔布（一种非甾体抗炎药）是常用于持续性疼痛的镇痛药，但具有中度胃肠道副作用或镇痛耐受性。一个有前途的镇痛策略是给予联合处方，允许最大或相等的疗效，副作用较少。在本研究中，在小鼠福尔马林疼痛模型中测试了度洛昔单抗和塞来昔布联合给药的疗效和副作用。皮下（s.c.）将福尔马林注射到左后爪中诱导显著的躯体和情感疼痛，分别通过注射福尔马林后1小时期间注射后爪的双相自发退缩和间期超声发声（USV）来评价。腹膜内（i. p.）在福尔马林注射前1h注射度洛昔布或塞来昔布可诱导对第二相而非第一相疼痛反应的剂量依赖性抑制。度洛昔单抗和塞来昔布联合给药对第二时相疼痛反应具有显著的镇痛作用。仅在较高剂量组合中观察到第一阶段的组合镇痛。观察到第二阶段疼痛反应的理论和实验ED 50之间的统计学差异，这表明两种药物的协同相互作用。关于USV显示的情感疼痛反应，我们假设抗伤害效应几乎完全来自度洛沙坦，因为塞来昔布单独给药无效，或联合给药时减少度洛沙坦的剂量。基于上述发现，度洛沙汀和塞来昔布急性联合给药对躯体疼痛行为而非情绪疼痛行为显示出协同作用。
Duloxetine, a serotonin and noradrenaline reuptake inhibitor, and celecoxib, a non-steroidal anti-inflammatory drug, are commonly used analgesics for persistent pain, however with moderate gastrointestinal side effects or analgesia tolerance. One promising analgesic strategy is to give a combined prescription, allowing the maximal or equal efficacy with fewer side effects. In the current study, the efficacy and side effects of combined administration of duloxetine and celecoxib were tested in the mouse formalin pain model. The subcutaneous (s.c.) injection of formalin into the left hindpaw induced significant somatic and emotional pain evaluated by the biphasic spontaneous flinching of the injected hindpaw and interphase ultrasonic vocalizations (USVs) during the 1 h after formalin injection, respectively. Pretreatment with intraperitoneal (i.p.) injection of duloxetine or celecoxib at 1 h before formalin injection induced the dose-dependent inhibition on the second but not first phase pain responses. Combined administration of duloxetine and celecoxib showed significant analgesia for the second phase pain responses. Combination analgesia on the first phase was observed only with higher dose combination. A statistical difference between the theoretical and experimental ED50 for the second phase pain responses was observed, which indicated synergistic interaction of the two drugs. Concerning the emotional pain responses revealed with USVs, we assumed that the antinociceptive effects were almost completely derived from duloxetine, since celecoxib was ineffective when administered alone or reduced the dosage of duloxetine when given in combination. Based on the above findings, acute concomitant administration of duloxetine and celecoxib showed synergism on the somatic pain behavior but not emotional pain behaviors.
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DOI：
10.1124/jpet.104.075960
发表时间：
2005-02-01
影响因子：
3.5
作者：
Jones, CK;Peters, SC;Shannon, HE
通讯作者：
Shannon, HE
影响因子：
2.5
作者：
Buvanendran, Asokumar;Kroin, Jeffrey S.
通讯作者：
Kroin, Jeffrey S.
影响因子：
2.9
作者：
ABBOTT, FV;GRIMES, RW;MELZACK, R
通讯作者：
MELZACK, R
影响因子：
3
作者：
Han, JS;Bird, GC;Neugebauer, V
通讯作者：
Neugebauer, V
影响因子：
2.9
作者：
Bardin, L.;Gregoire, S.;Depoortere, R.
通讯作者：
Depoortere, R.