CHARACTERIZATION OF TIME-COURSE OF SPINAL AMINO-ACIDS, CITRULLINE ANDPGE(2) RELEASE AFTER CARRAGEENAN KAOLIN-INDUCED KNEE-JOINT INFLAMMATION - A CHRONIC MICRODIALYSIS STUDY/

Pharmacological studies have implicated the spinal activation of excit atory amino acids, nitric oxide, and prostaglandins systems in the dev elopment of tactile and thermal hypersensitivity and central sensitiza tion after peripheral inflammation. In the present study, using a chro nically placed loop dialysis catheter, we examined in the unanesthetiz ed rat the effect of carrageenan/kaolin (C/K)-induced knee joint infla mmation 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 E(2) (PGE(2)) a s well as the concomitant development of tactile and thermal hypersens itivity. Infection of C/K in the knee evoked a significant release of glutamate, with an initial peak seen immediately after knee C/K inject ion (179 +/- 22%) and with a progressive and consistent increase over a period of 24 h (153-186%). Comparable changes in the concentration o f aspartate (123-179%) were observed. Citrulline was constantly above baseline for the 24-h period (121-158%). PGE(2) was significantly incr eased at 10 min (146 +/- 11%) with no change observed between 3-5 h. A t 24 h, PGE(2) was again significantly (143 +/- 18%) increased. Behavi orally, a prominent thermal and tactile allodynia developed after inje ction with the peak seen by 1-3 h after induction of the inflammation. This hypersensitivity state, while diminished in its intensity, persi sted for the entire observation period. These data suggest that increa sed spinal release of excitatory amino acids (EAA), nitric oxide and/o r PGE(2) is involved in the maintenance of the pain state initiated by acute peripheral inflammation.