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 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.
Malmberg
Annika B
AB
Department of Anesthesiology, University of California, San Diego, La Jolla, CA 92093-0818 USA Department of Clinical Pharmacology, Sahlgrenska University Hospital, Göteborg, Sweden.
Yaksh
Tony L
TL
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005557:Formaldehyde / Q000494:pharmacology; D006358:Hot Temperature; D007278:Injections, Spinal; D009020:Morphine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020960:omega-Conotoxins
D002121:Calcium Channel Blockers; D010455:Peptides; D020960:omega-Conotoxins; D005557:Formaldehyde; D009020:Morphine; C078452:ziconotide