Pharmacological assessment of the rat formalin test utilizing the clinically used analgesic drugs gabapentin, lamotrigine, morphine, duloxetine, tramadol and ibuprofen: Influence of low and high formalin concentrations
Pharmacological assessment of the rat formalin test utilizing the clinically used analgesic drugs gabapentin, lamotrigine, morphine, duloxetine, tramadol and ibuprofen: Influence of low and high formalin concentrations
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DOI：
10.1016/j.ejphar.2009.01.004
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发表时间：
2009-03-01
影响因子：
5
通讯作者：
Munro, Gordon
中科院分区：
文献类型：
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作者：
Munro, Gordon
福尔马林试验用作测定化合物在实验室啮齿动物中的抗伤害感受活性的主要行为筛选。后爪福尔马林注射后，伤害性行为以双相模式表达，并与注射的福尔马林浓度密切相关。在此，在用1%或5%福尔马林注射的大鼠中比较了用于慢性疼痛的临床治疗的六种化合物的抗伤害感受功效。可以预见的是，抗炎药布洛芬（30-300 mg/kg）减弱了5%福尔马林注射大鼠的第二阶段（16-40 min）伤害感受行为; 1%福尔马林注射大鼠不受影响。抗癫痫药物加巴喷丁（50-200 mg/kg）和拉莫三嗪（10-60 mg/kg）在1%和5%试验中仅在第二相具有抗伤害性。值得注意的是，它们在1%与5%福尔马林注射大鼠中的效力是2-4倍。双重单胺再摄取抑制剂度洛昔单抗（3-60 mg/kg）在两项试验的第一阶段和间期持续减弱伤害性行为。然而，第二阶段伤害性感受仅在5%福尔马林注射的大鼠中减弱，与1%福尔马林注射的大鼠相比，效力增加6倍。β-阿片受体激动剂吗啡（1-6 mg/kg）和组合β-阿片受体激动剂/单胺再摄取抑制剂曲马多（5-50 mg/kg）在1%和5%试验期间均减弱伤害性行为：在第二阶段，任一化合物的抗伤害性效力均无差异。因此，对于机械上不同的化合物，福尔马林试验的预测性抗伤害感受能力可以随着注射的福尔马林浓度而变化，这可能是外周和中枢伤害感受信号传导机制差异参与的结果。(C)2009爱思唯尔有限公司版权所有。
The formalin test is used as a primary behavioural screen for assaying the antinociceptive activity of compounds in laboratory rodents. After hindpaw formalin injection, nociceptive behaviours are expressed in a biphasic pattern and correlate closely with the concentration of formalin injected. Here, the antinociceptive efficacy of six compounds used in the clinical treatment of chronic pain was compared in rats injected with either 1% or 5% formalin. Predictably, the anti-inflammatory drug ibuprofen (30-300 mg/kg) attenuated second phase (16-40 min) nociceptivebehaviours in 5% formalin-injected rats; 1% formalin-injected rats were unaffected. The anti-epileptic drugs gabapentin (50-200 mg/kg) and lamotrigine (10-60 mg/kg) were anti nociceptive only during second phase in both 1% and 5% tests. Notably, they were 2-4 times more potent in 1% vs 5% formalin-injected rats. The dual monoamine reuptake inhibitor duloxetine (3-60 mg/kg) consistently attenuated nociceptive behaviours during first phase and interphase in both tests. However second phase nociception was only attenuated in 5% formalin-injected rats giving rise to a 6 fold increase in potency compared with 1% formalin-injected rats. The p-opioid receptor agonist morphine (1-6 mg/kg) and the combined p-opioid receptor agonist/monoamine reuptake inhibitor tramadol (5-50 mg/kg) both attenuated nociceptive behaviours throughout the duration of both the 1% and 5% tests: no difference in antinociceptive potency occurred for either compound during second phase. Thus, for mechanistically-distinct compounds the predictive antinociceptive capacity of the formalin test can vary with the concentration of formalin injected, likely as a result of peripheral and central nociceptive signalling mechanisms being differentially engaged. (C) 2009 Elsevier B.V. All rights reserved.