Enhancement of antinociceptive effect of fentanyl by KB-2796 at spinal level

Opioids inhibit the voltage-dependent calcium channel conductance, which is one of the mechanisms of opioid analgesia on the opioid receptor. According to the hypothesis that calcium antagonists can potentiate the analgesic effect of opioids, we designed a study to investigate the effects of KB-2796, a new calcium channel blocker, on the antinociception of fentanyl at the level of the spinal cord in rats. PE-10 catheters were chronically implanted in the lumbar intrathecal space of the rats. Tail-flick test was used to assess the nociceptive sensitivity. Fentanyl (1 microgram) and KB-2796 (50, 150 or 250 micrograms) were tested individually as well as in combination. Dimethyl sulfoxide (10%) was used as a control. All drugs were injected intrathecally. Fentanyl alone produced a significant but short duration (15-30 minutes) of antinociception. KB-2796 by itself did not show any antinociception at any of the doses tested. However, when KB-2796 at the higher doses (150 and 250 micrograms) was administered with fentanyl, the antinociceptive effect was significantly (P < 0.05) enhanced over that of fentanyl alone from 30 to 180 minutes after the injection. In conclusion, our results suggest that KB-2796 potentiates the analgesic effect of fentanyl at the spinal level. These data also support our hypothesis that calcium channel blockers may involve in the antinociception of opioids.