Antinociceptive mechanisms of Dipsacus saponin C administered intrathecally in mice

Dipsacus saponin C (DSC) administered intrathecally (i.t.) showed antinocic eptive effect in a dose-dependent (from 3.75 to 30 mu g) manner as measured by the tail-flick assay. The antinociception induced by DSC at the dose of 30 mu g reached at peak 7.5 min and almost returned to the control level a fter 60 min. 5-Amino-valeric acid (5-AVA, a GABA(A) receptor antagonist, fr om 1 to 20 mu g) and SR 95531 (a GABA(B) receptor antagonist, from 0.1 to 2 ng) dose-dependently attenuated i.t, administered DSC-induced increase of the inhibition of the tail-flick response. The i.t. injection of yohimbine (an alpha(2)-adrenergic receptor antagonist, from 1 to 20 mu g) and methyse rgide (a serotonin receptor antagonist, from 1 to 20 mu g), but not naloxon e (from 2 to 8 mu g), significantly attenuated inhibition of the tail-flick response induced by DSC (30 mu g) administered i.t. Sulfated cholecystokin in (CCK, from 0.05 to 0.5 ng) injected i.t. significantly reduced the inhib ition of the tail-flick response induced by DSC (30 mu g) administered i.t. Our results suggest that DSC shows an antinociceptive effect when it is ad ministered spinally and GABA(A), GABA(B), alpha(2)-adrenergic and serotonin receptors located at the spinal cord level, but not opioid receptors, may be involved in DSC-induced antinociception. Furthermore, CCK may play an im portant role for the modulation of i.t. injected DSC-induced antinociceptio n. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.