Effect of continuous intrathecal infusion of ω-conopeptides, N-type calcium-channel blockers, on behavior and antinociception in the formalin and hot-plate tests in rats

Abstract

The effect of continuous intrathecal infusion of omega-conopeptides in the rat was examined to determine whether antinociception, as measured on the formalin and hot-plate (52.5 degrees C) tests, was altered and whether tolerance developed with chronic infusion of these agents. Infusion 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 compared to the effect of 20 nmol/h morphine or saline. Both doses of SNX-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 compared to saline infusion. In contrast, morphine only produced a significant effect on day 2, but not on infusion day 7, indicating that tolerance had developed. The effect of SNX-111 was reversible, as shown by a return to nociceptive responses similar to saline-infused rats 2 days after the minipumps had been disconnected after a 7-day infusion period. These data indicate that chronic infusion of omega-conopeptides that block N-type voltage-sensitive calcium channels produce a powerful antinociception, with minimal development of tolerance.