Excitatory amino acid profiles of synovial fluid from patients with arthritis

Objective. Previous studies in an experimental synovitis model in rats dete rmined that administration of glutamate and aspartate into the joint produc es hyperalgesic responses, while their receptor antagonists provide protect ion against the development of a hyperalgesic state. We examined concentrat ions of amino acids in synovial fluid (SF) to determine if increases might be relevant to human joint pathology. Methods. One hundred forty-four repository SF samples from patients undergo ing diagnostic or therapeutic arthrocentesis and 14 SF samples from 7 cadav ers were analyzed by high pressure liquid chromatography and compared as ar thritic and control cohorts. Results. Compared to the average concentrations from the autopsy cases, the excitatory amino acids (EAA) glutamate and aspartate in SF from patients w ith synovitis were 54 and 28 times higher, respectively. Increases for all other amino acids ranged from 3 to 18-fold, The values for glutamate and as partate were significantly higher than the mean increase for other amino ac ids compared using unpaired t tests (p < 0.0001). The mean ratio of glutama te and aspartate elevations over the mean increase for other amino acids wa s 4-fold and 2-fold, respectively. The EAA were highest in Reiter's, infect ious arthropathies, and systemic lupus erythematosus, but did not appreciab ly segregate to diagnosis or SF white blood cell count. Conclusion. Our data provide evidence of increased glutamate and aspartate in the SF of humans with active arthritis, suggesting that glutamate mediat ed events may contribute to the pathogenesis of human arthritic conditions.