Shock titration in the rhesus monkey: effects of opiate and nonopiate analgesics

This study evaluated the antinociceptive effects of several opiate and nonopiate analgesics in the rhesus monkey using a discrete trial shock titration paradigm. Morphine sulfate (1, 5 and 10 mg/kg i.m.) and codeine sulfate (3, 10 and 30 mg/kg i.m.) produced a significant and dose-dependent increase in mean shock threshold that was not accompanied by a significant increase in mean response latency. The mean number of shocks terminated was significantly decreased at the highest dose of each opiate. Aspirin (100 and 300 mg/kg p.o.) or ibuprofen (200 mg/kg p.o.) did not significantly increase mean shock threshold or mean response latency or decrease mean number of shocks terminated. However, 6 mg/kg i.m. of 4,5,6,7-tetrahydroisoxazolo [5,4-c]pyridin-3-ol produced a significant increase in mean shock threshold and mean response latency with no significant effect on mean number of shocks terminated. The absence of any effects of a 2-mg/kg dose of 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol and the severe side effects produced by 10 mg/kg prevented determination of its dose-response relationship. Diazepam (0.5, 2 and 8 mg/kg i.m.) produced a significant, dose-dependent increase in mean shock threshold and a significant increase in mean response latency with no consistent or significant effect on mean number of shocks terminated. Doses of 2 and 8 mg/kg of diazepam also produced signs of ataxia. These results suggest that the discrete trial shock titration paradigm is suitable for demonstration of the antinociceptive effects of opiate and certain nonopiate analgesics, but not nonsteroidal anti-inflammatory analgesics in the rhesus monkey.