Behavioural and electrophysiological evidence for an analgesic effect of a non-steroidal anti-inflammatory agent, sodium diclofenac.
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.
Attal
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Unité de Recherches de Neurophysiologie Pharmacologique, U161 INSERM, 2 rue d'Alésia, 75014 ParisFrance.
Kayser
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V
Eschalier
A
A
Benoist
J M
JM
Guilbaud
G
G
D000200:Action Potentials; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001168:Arthritis / Q000188:drug therapy* / Q000503:physiopathology; D004008:Diclofenac / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D008297:Male; D010146:Pain / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D010147:Pain Measurement; D051381:Rats; D011919:Rats, Inbred Strains; D013787:Thalamic Nuclei / Q000187:drug effects / Q000503:physiopathology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac