Evidence for spinal N-methyl-D-aspartate receptor involvement in prolonged chemical nociception in the rat

Brain Res. 1990 Jun 4;518(1-2):218-26. doi: 10.1016/0006-8993(90)90975-h.


Subcutaneous injection of formalin into the hindpaw peripheral receptive field of deep dorsal horn multireceptive (convergent) nociceptive neurones was used to produce a prolonged (1 h) activation of the cells. This chemical noxious stimulus produced a first peak of firing which lasted 10 min followed by a second peak of prolonged activity which was monitored for 50 min. gamma-D-glutamylglycine (DGG), a non-selective N-methyl-D-aspartate (NMDA) and quisqualate/kainate (non-NMDA) receptor antagonist was applied intrathecally both as a pretreatment and after the formalin. A complete abolition of both peaks of the formalin response was produced by DGG pretreatment (1000 micrograms) (n = 4). This dose produced profound inhibition of the acute C-fibre evoked responses of the same cells. However, no inhibitions were produced when the antagonist was applied once the formalin response had developed (n = 4). The selective NMDA receptor antagonist 5-amino-phosphonovaleric acid (AP5) was administered intrathecally (250 and 500 micrograms) as a 40 min pretreatment and caused a small inhibition of the first peak but a marked dose-related reduction in the second prolonged phase (n =7). AP5 did not influence the C-fibre inputs onto the cells. The non-competitive NMDA receptor channel blockers, ketamine and MK801, were administered i.v. during the second phase of firing. Ketamine (1-8 mg/kg) caused a short-lasting but marked and dose-related inhibition of the neuronal responses to formalin (n = 11). MK801 (0.5-1 mg/kg) resulted in a prolonged inhibition of cell firing during the second phase of the response (n = 11).(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Amino-5-phosphonovalerate / pharmacology*
  • Animals
  • Dibenzocycloheptenes / pharmacology
  • Dipeptides / pharmacology*
  • Dizocilpine Maleate
  • Electric Stimulation
  • Formaldehyde
  • Ketamine / pharmacology
  • Neurons / drug effects
  • Neurons / physiology*
  • Nociceptors / physiology
  • Pain / physiopathology*
  • Rats
  • Rats, Inbred Strains
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Neurotransmitter / drug effects
  • Receptors, Neurotransmitter / physiology*
  • Spinal Cord / drug effects
  • Spinal Cord / physiology*


  • Dibenzocycloheptenes
  • Dipeptides
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Neurotransmitter
  • gamma-glutamylglycine
  • Formaldehyde
  • Ketamine
  • Dizocilpine Maleate
  • 2-Amino-5-phosphonovalerate