Antinociceptive Mechanisms of Platycodin D Administered Intracerebroventricularly in the Mouse

Abstract

Platycodin D administered intracerebroventricularly (i. c. v.) showed an antinociceptive effect in a dose-dependent manner as measured by the tail-flick assay. The antinociception induced by platycodin D was maintained at least 1 h. MK-801 [(±)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate], a competitive N-methyl-D-aspartic acid (NMDA) receptor antagonist, or CNQX (6-cyano-7-nitroquinoxaline-2,3-dione), a non-NMDA receptor antagonist, muscimol (a GABA_A receptor agonist), or baclofen (a GABA_B receptor antagonist), or sulfated cholecystokinin (CCK-8 s; CCK_A receptor agonist), injected i. c. v. significantly reduced the inhibition of the tail-flick response induced by platycodin D administered i. c. v. Additionally, intrathecal (i. t.) pretreatment with yohimbine (an α₂-adrenergic receptor antagonist) or methysergide (a serotonin receptor antagonist) dose-dependently attenuated inhibition of the tail-flick response induced by i. c. v. administered platycodin D. However, naloxone (an opioid receptor antagonist) did not affect the inhibition of the tail-flick response induced by platycodin D. Our results suggest that platycodin D has an antinociceptive effect when it is administered supraspinally, and supraspinal GABA_A, GABA_B, NMDA and non-NMDA receptors are involved in platycodin D-induced antinociception. Furthermore, platycodin D administered supraspinally produces antinociception by stimulating descending noradrenergic and serotonergic, but not opioidergic, pathways.

Platycodin D - Platycodon grandiflorum - Campanulaceae - antinociception - glutamate receptor - GABA receptor - CCK receptor - descending pain inhibitory system

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