Behavioural and electrophysiological evidence for an analgesic effect of a non-steroidal anti-inflammatory agent, sodium diclofenac

Abstract

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.