Evoked Release of Amino Acids and Prostanoids in Spinal Cords of Anesthetized Rats: Changes During Peripheral...

C-fiber stimulation of the sciatic nerve in rats with an acute experimental arthritis elicited a greatly enhanced spinal release of several amino acids and prostaglandin PGE(2) (PGE(2)) when compared to control rats. The most dramatic change was in aspartate (Asp) which was not released in the control state but did increase significantly for a period outlasting the stimulation in the animals with knee joint inflammation. Evoked release of Glu, Gly, and PGE(2) also increased in the experimental group. It is proposed that the Asp acts primarily at N-methyl-D-asparate (NMDA) receptors to participate in the generation of hyperalgesia. In a similar model, direct activation of the NMDA receptors evoked spinal release of the same amino acids, including citrulline (an index of nitric oxide production) as well as representative prostanoids. Pretreatment with a NO synthase inhibitor blocked the release of Cit and Glu and reduced PGE(2) release evoked by NMDA, indicating that 1) Glu release is downstream of the actions of NO, and 2) the cyclooxygenase system is not independent of NO production. Evoked release of thromboxane B(2) was not affected by pretreatment with the nitric oxide synthesis inhibitor. Pretreatment with a cyclooxygenase inhibitor antagonized release of both prostanoids, but had little effect on NMDA-evoked increases in amino acids and Cit.