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

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Abstract
Nd 0.003 nmol/h SNX-111 and 0.290 nmol/h SNX-239 was performed for either 2 days (‘acute’) or 7 days (‘chronic’) 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 ω-conopeptides that block N-type voltage-sensitive calcium channels produce a powerful antinociception, with minimal development of tolerance. ∗Corresponding author: Annika B. Malmberg, Department of Clinical Pharmacology, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden. Tel.: (46) 31-773-3421 or (46) 31-602974; FAX: (46) 31-773-3422 or (46) 31-826723. (Received 2 February 1994; revision received 14 April 1994; accepted 21 April 1994.) © Lippincott-Raven Publishers....