Antinociceptive effects of non-steroidal anti-inflammatory drugs in a rat model of unilateral hindpaw inflammation.
The antinociceptive activity of intramuscular 6-methoxy-2-naphthylacetic acid (6-MNA), the active metabolite of nabumetone, was examined in a rat model of unilateral hindpaw inflammation/hyperalgesia and compared with that of three other non-steroidal anti-inflammatory drugs (NSAIDs)--diclofenac, naproxen and piroxicam. Over a dose range of 10-100 mg/kg i.m., 6-MNA produced a dose-dependent increase in the withdrawal threshold to a noxious mechanical stimulus applied to the inflamed paw; however, a higher dose (300 mg/kg) produced no further increase in antinociceptive activity. Peak effects occurred 30 min after intramuscular injection. Diclofenac, naproxen and piroxicam produced antinociceptive effects that were qualitatively similar to those of 6-MNA. There was an indication of quantitative differences between the four NSAIDs in terms of potency and efficacy although this was not statistically significant. The rapid onset of effect and the lack of correlation between the relative antinociceptive effects of the four NSAIDs and the anti-inflammatory activities (assayed as inhibition of carrageenan-induced rat paw oedema) suggest that their pain relieving properties may not be entirely the result of their anti-inflammatory effects. These experimental data support the therapeutic value of 6-MNA as an analgesic in conditions of inflammatory pain.
Clarke
G D
GD
Department of Biology, SmithKline Beecham Farmaceutici, Milan, Italy.
MacPherson
I S
IS
Petrone
G
G
Spangler
R S
RS
D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D004008:Diclofenac / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D007249:Inflammation / Q000503:physiopathology*; D007273:Injections, Intramuscular; D008297:Male; D009280:Naphthaleneacetic Acids / Q000627:therapeutic use*; D009288:Naproxen / Q000627:therapeutic use; D010146:Pain / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D009280:Naphthaleneacetic Acids; D004008:Diclofenac; D009288:Naproxen; C044612:6-methoxy-2-naphthylacetic acid