NR2B containing NMDA receptor dependent windup of single spinal neurons

Neuropharmacology. 2004 Jan;46(1):23-30. doi: 10.1016/s0028-3908(03)00339-3.


Windup, the frequency dependent build-up of spinal neuronal responses, is implicated in the development of central sensitization of nociceptive pathways. N-methyl-D-aspartate (NMDA) receptors have been shown to be involved in these processes but the role of various receptor subtypes at the spinal level is not fully understood. In our experiments, we compared the inhibitory effect of MK-801 (a nonselective NMDA receptor antagonist, 0.01-3 mg/kg i.v.) and CI-1041 (an NR2B subunit specific NMDA receptor antagonist, 0.3-10 mg/kg i.v.) on the formation of dorsal horn neuronal windup in spinalized rats, in vivo. Both types of antagonist blocked windup considerably at doses not affecting the normal synaptic transmission. These results are in agreement with the well-documented effectivity of NR2B subtype selective NMDA receptor antagonists in chronic pain models and give the first direct evidence that spinal mechanisms are involved in this effect.

Publication types

  • Comparative Study

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / radiation effects
  • Analysis of Variance
  • Animals
  • Benzoxazoles / pharmacology
  • Dizocilpine Maleate / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Electric Stimulation / methods
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / radiation effects
  • Male
  • Nerve Fibers / drug effects
  • Nerve Fibers / radiation effects
  • Piperidines / pharmacology
  • Posterior Horn Cells / drug effects
  • Posterior Horn Cells / physiology*
  • Posterior Horn Cells / radiation effects
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Spinal Cord / cytology*
  • Spinal Cord Injuries / physiopathology


  • Benzoxazoles
  • Excitatory Amino Acid Antagonists
  • NR2B NMDA receptor
  • Piperidines
  • Receptors, N-Methyl-D-Aspartate
  • besonprodil
  • Dizocilpine Maleate