Characterization of time course of spinal amino acids, citrulline and PGE2 release after carrageenan/kaolin-induced knee joint inflammation: a chronic microdialysis study

Pain. 1996 Oct;67(2-3):345-54. doi: 10.1016/0304-3959(96)03106-5.


Pharmacological studies have implicated the spinal activation of excitatory amino acids, nitric oxide, and prostaglandins systems in the development of tactile and thermal hypersensitivity and central sensitization after peripheral inflammation. In the present study, using a chronically placed loop dialysis catheter, we examined in the unanesthetized rat the effect of carrageenan/kaolin (C/K)-induced knee joint inflammation on the time course of spinal release of several active factors including excitatory amino acids (glutamate, aspartate), citrulline (a marker of nitric oxide formation), and prostaglandin E2 (PGE2) as well as the concomitant development of tactile and thermal hypersensitivity. Infection of C/K in the knee evoked a significant release of glutamate, with an initial peak seen immediately after knee C/K injection (179 +/- 22%) and with a progressive and consistent increase over a period of 24 h (153-186%). Comparable changes in the concentration of aspartate (123-179%) were observed. Citrulline was constantly above baseline for the 24-h period (121-158%). PGE2 was significantly increased at 10 min (146 +/- 11%) with no change observed between 3-5 h. At 24 h, PGE2 was again significantly (143 +/- 18%) increased. Behaviorally, a prominent thermal and tactile allodynia developed after injection with the peak seen by 1-3 h after induction of the inflammation. This hypersensitivity state, while diminished in its intensity, persisted for the entire observation period. These data suggest that increased spinal release of excitatory amino acids (EAA), nitric oxide and/or PGE2 is involved in the maintenance of the pain state initiated by acute peripheral inflammation.

MeSH terms

  • Amino Acids / metabolism*
  • Animals
  • Arthritis / chemically induced
  • Arthritis / metabolism*
  • Arthritis / physiopathology
  • Carrageenan
  • Citrulline / metabolism*
  • Dinoprostone / metabolism*
  • Drug Combinations
  • Hot Temperature
  • Injections, Intra-Articular
  • Kaolin
  • Male
  • Microdialysis
  • Physical Stimulation
  • Rats
  • Rats, Sprague-Dawley
  • Sodium Chloride / pharmacology
  • Spinal Cord / metabolism*
  • Time Factors
  • Touch


  • Amino Acids
  • Drug Combinations
  • Kaolin
  • Citrulline
  • Sodium Chloride
  • Carrageenan
  • Dinoprostone