Determination of analgesic drug efficacies by modification of the Randall and Selitto rat yeast paw test.
This report describes a modified Randall and Selitto (1957) rat yeast paw test that can evaluate differences in efficacy of different analgesics. The modifications consist of a decrease in the rate of acceleration of the noxious stimulus (mechanical pressure) on the inflamed paw from 20 to 12.5 mmHg/sec and an extension of the cut-off time from 15 to 60 sec. All the narcoticlike drugs tested (morphine, codeine, and pentazocine) increased the response latencies of the inflamed paws to the cut-off time. The nonsteroidal antiinflammatory-like drugs tested (acetylsalicylic acid, acetaminophen, indomethacin, phenylbutazone, and proquazone) showed plateaus in their analgesic effects (i.e., increasing the dose failed to produce significantly greater increases in the response latencies compared to the next lower dose). Zomepirac (80-240 mg/kg p.o.) did not show this plateau effect, but was unable to increase response latencies to greater than 30 sec because of the toxicity of higher doses (320 mg/kg p.o.). Flunixin NMG (the meglumine salt of flunixin), a nonnarcotic analgesic, did not display a plateau effect and increased response latencies to maximum values. The methodology was therefore able to discriminate analgesics active against mild to severe clinical pain (narcoticlike) from those only useful against mild to moderate pain (nonnarcotic-like).
D000700:Analgesics / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D005121:Extremities; D008297:Male; D008722:Methods; D051381:Rats; D011919:Rats, Inbred Strains; D015002:Yeast, Dried
D000700:Analgesics; D000701:Analgesics, Opioid; D000894:Anti-Inflammatory Agents, Non-Steroidal