Down-regulation of NR2B receptors partially contributes to analgesic effects of Gentiopicroside in persistent inflammatory pain

Neuropharmacology. 2008 Jun;54(8):1175-81. doi: 10.1016/j.neuropharm.2008.03.007. Epub 2008 Mar 25.


Gentiopicroside is one of the secoiridoid compound isolated from Gentiana lutea. It exhibits analgesic activities in the mice. The anterior cingulate cortex (ACC) is a forebrain structure known for its roles in pain transmission and modulation. Painful stimuli potentiate the prefrontal synaptic transmission and induce glutamate NMDA NR2B receptor expression in the ACC. But little is known about Gentiopicroside on the persistent inflammatory pain and chronic pain-induced synaptic transmission changes in the ACC. The present study was undertaken to investigate its analgesic activities and central synaptic modulation to the peripheral painful inflammation. Gentiopicroside produced significant analgesic effects against persistent inflammatory pain stimuli in mice. Systemic administration of Gentiopicroside significantly reversed NR2B over-expression during the chronic phases of persistent inflammation caused by hind-paw administration of complete Freunds adjuvant (CFA) in mice. Whole-cell patch clamp recordings revealed that Gentiopicroside significantly reduced NR2B receptors mediated postsynaptic currents in the ACC. Our findings provide strong evidence that analgesic effects of Gentiopicroside involve down-regulation of NR2B receptors in the ACC to persistent inflammatory pain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Non-Narcotic*
  • Animals
  • Blotting, Western
  • Chronic Disease
  • Cyclic AMP / metabolism
  • Down-Regulation / drug effects
  • Excitatory Postsynaptic Potentials / drug effects
  • Freund's Adjuvant
  • Glucosides / pharmacology*
  • Glucosides / therapeutic use*
  • Glutamic Acid / physiology
  • Inflammation / chemically induced
  • Inflammation / complications*
  • Inflammation / drug therapy*
  • Iridoid Glucosides
  • Iridoids / pharmacology*
  • Iridoids / therapeutic use*
  • Mice
  • Mice, Inbred C57BL
  • Pain / drug therapy*
  • Pain / etiology*
  • Pain / psychology
  • Pain Measurement / drug effects
  • Patch-Clamp Techniques
  • Receptors, GABA-A / drug effects
  • Receptors, N-Methyl-D-Aspartate / biosynthesis*
  • Synaptic Transmission / drug effects


  • Analgesics, Non-Narcotic
  • Glucosides
  • Iridoid Glucosides
  • Iridoids
  • NR2B NMDA receptor
  • Receptors, GABA-A
  • Receptors, N-Methyl-D-Aspartate
  • gentiopicroside
  • Glutamic Acid
  • Freund's Adjuvant
  • Cyclic AMP