The role of nitric oxide and prostaglandin E-2 on the hyperalgesia inducedby excitatory amino acids in rats

The present study was designed to investigate the role of nitric oxide (NO) , N-methyl-D-aspartate (NMDA) receptor and prostaglandins on hyperalgesia i nduced in rats by excitatory amino acids and the possibility that prostagla ndins may act as the retrograde messenger in the spinal cord like NO. N omega-nitro-L-arginine methyl ester (L-NAME; 500 mu g/paw, intraplantarly (i.pl.)), MK-801 (10 mu g/paw, i.pl.) or indomethacin (300 mu g/paw, i.pl. ) reduced the duration of phase 2 of the biting/licking and scratching (B/L + S) response induced by formalin injection from 255.6+/-16.7s to 155.6+/- 16.9, 172.2+/-33.3 or 205.6+/-16.7s, respectively. L-NAME (0.3 mg, i.th.), MK-801 (8 mu g, i.th.) or indomethacin (20 ug, i.th) reduced the duration o f phase 2 of the B/L+S response induced by saline injection from 288.5+/-7. 7s to 207.7+/-19.2, 184.6+/-7.7 or 192.3+/-38.5 s, respectively. L-NAME or indomethacin injected into the spinal cord of the rat significantly reduced the hyperalgesia induced by NMDA (1 mu g, i.th.) from 43.8+/-4.6% to 12.3/-3.1 and 19.2+/-2.3%, respectively. It is assumed that NO produced by exci tatory amino acids may increase prostaglandin production by cyclooxygenase activation. L-NAME, MK-801 or indomethacin injected into the rat spinal cord significan tly reduced the hyperalgesia induced by prostaglandin E-2 (PGE(2), 25 ng, i .th.) in the tail-flick test from 40.6+/-3.5% to 18.2+/-3.2, 18.8+/-1.8 or 17.6+/-4.1%, respectively, but had little effect on hyperalgesia in the paw pressure test (except for indomethacin). In conclusion, NO and PGE2 affect the hyperalgesia induced by excitatory am ino acids. It is suggested that PGE2, like NO, may act as a retrograde mess enger in the spinal cord.