Attal N, Kayser V, Eschalier A, Benoist J M, Guilbaud G
Unité de Recherches de Neurophysiologie Pharmacologique, U161 INSERM, 2 rue d'Alésia, 75014 ParisFrance.
Pain. 1988 Dec;35(3):341-348. doi: 10.1016/0304-3959(88)90143-1.
The effects of various i.v. doses of diclofenac sodium (Voltaren, 1.5, 3, 6 and 9 mg/kg) were evaluated by measuring the vocalization threshold in response to paw pressure in normal and in Freund's adjuvant-induced arthritic rats. An electrophysiological study performed in parallel in arthritic rats considered the effects of 6 mg/kg i.v. diclofenac on ventrobasal thalamic neuronal responses driven by mild stimulation of an inflamed joint. In normal rats, 6 and 9 mg/kg i.v. diclofenac raised vocalization thresholds significantly (maximum vocalization thresholds were respectively 135.67 +/- 3.30% and 157.41 +/- 4.62% of the preinjection control at 30 min, n = 9 in each group), while no effect was observed with 3 mg/kg. In arthritic rats, i.v. doses of 3, 6 and 9 mg/kg diclofenac induced a clear analgesic effect (maximum vocalization thresholds were respectively 172.22 +/- 4.26, 201.78 +/- 4.76, 222.33 +/- 5.10% of the control at 25 min, n = 9 in each group), whereas a dose of 1.5 mg/kg i.v. did not raise the threshold. In arthritic rats, the VB neuronal responses were depressed by about 50% 20 min after an injection of 6 mg/kg i.v. diclofenac. These results clearly establish that diclofenac produces a dose-dependent analgesic effect, which is more potent in arthritic than in normal rats.
通过测量正常大鼠和弗氏佐剂诱导的关节炎大鼠对爪部压力的发声阈值，评估了不同静脉注射剂量双氯芬酸钠（扶他林，1.5、3、6和9毫克/千克）的效果。在关节炎大鼠中同时进行的电生理研究考察了静脉注射6毫克/千克双氯芬酸钠对轻度刺激发炎关节所驱动的腹侧基底丘脑神经元反应的影响。在正常大鼠中，静脉注射6毫克/千克和9毫克/千克双氯芬酸钠可显著提高发声阈值（30分钟时最大发声阈值分别为注射前对照的135.67±3.30%和157.41±4.62%，每组n = 9），而3毫克/千克剂量未观察到效果。在关节炎大鼠中，静脉注射3毫克/千克、6毫克/千克和9毫克/千克双氯芬酸钠可产生明显的镇痛作用（25分钟时最大发声阈值分别为对照的172.22±4.26%、201.78±4.76%、222.33±5.10%，每组n = 9），而静脉注射1.5毫克/千克剂量未提高阈值。在关节炎大鼠中，静脉注射6毫克/千克双氯芬酸钠20分钟后，腹侧基底丘脑神经元反应降低约50%。这些结果清楚地表明，双氯芬酸钠产生剂量依赖性镇痛作用，在关节炎大鼠中比在正常大鼠中更有效。
