EFFECT OF CONTINUOUS INTRATHECAL INFUSION OF OMEGA-CONOPEPTIDES, N-TYPE CALCIUM-CHANNEL BLOCKERS, ON BEHAVIOR AND ANTINOCICEPTION IN THE FORMALIN AND HOT-PLATE TESTS IN RATS

The effect of continuous intrathecal infusion of omega-conopeptides in the rat was examined to determine whether antinociception, as measure d on the formalin and hot-plate (52.5 degrees C) tests, was altered an d whether tolerance developed with chronic infusion of these agents. I nfusion of 0.030 and 0.003 nmol/h SNX-111 and 0.290 nmol/h SNX-239 was performed for either 2 days ('acute') or 7 days ('chronic') and was c ompared to the effect of 20 nmol/h morphine or saline. Both doses of S NX-111 and SNX-239 produced a significant reduction of the response to the hot-plate and formalin tests at both 2 and 7 days of infusion com pared to saline infusion. In contrast. morphine only produced a signif icant effect on day 2, but not on infusion day 7, indicating that tole rance had developed. The effect of SNX-111 was reversible, as shown by a return to nociceptive responses similar to saline-infused rats 2 da ys after the minipumps had been disconnected after a 7-day infusion pe riod. These data indicate that chronic infusion of omega-conopeptides that block N-type voltage-sensitive calcium channels produce a powerfu l antinociception, with minimal development of tolerance.