Antinociceptive mechanisms of Dipsacus saponin C administered intracerebroventricularly in the mouse

Abstract

1. 1. Dipsacus saponin C (DSC) administered intracerebroventricularly (ICV) showed an antinociceptive effect in a dose-dependent (from 3.75 to 30 μg) manner as measured by the tailflick assay. The antinociception induced by DSC at the dose of 30 μg was maintained at least I h. 2. 2. Sulfated cholecystokinin (CCK, from 0.1 to 0.5 ng); muscimol (a GABA A receptor agonist, from 50 to 200 ng); MK-801 [(±)-5-methyl-10, 11-dihydro-5H-dibenzo (a,d) cyclohepten-5, 10-imine maleate, from 0.1 to 1 μg], a noncompetitive N-methyl- d-aspartic acid (NMDA) receptor antagonist; or CNQX (6-cyano-7-nitroquinoxaline-2,3-dione, from 0.1 to 0.5 μg), a non-NMDA receptor antagonist, injected ICV significantly reduced the inhibition of the tail-flick response induced by DSC (30 μg) administered ICV. However, naloxone (an opioid receptor antagonist, 2 μg) or baclofen (a GABA B receptor antagonist, 10 ng) did not affect the inhibition of the tail-flick response induced by DSC. 3. 3. The intrathecal (IT) injection of yohimbine (an α 2-adrenergic receptor antagonist, from 5 to 20 μg) and methysergide (a serotonin receptor antagonist, from 5 to 20 μg) but not naloxone (from 2 to 8 μg), significantly attenuated inhibition of the tail-flick response induced by DSC (30 μg) administered ICV. 4. 4. Our results suggest that DSC has an antinociceptive effect when it is administered supraspinally and GABA A, NMDA and non-NMDA receptors, but not opioid and GABA B receptors located at the supraspinal level, may be involved in DSC-induced antinociception. Furthermore, DSC administered supraspinally may produce antinociception by stimulating descending α 2-adrenergic and serotonin pathways but not the opioidergic pathway.