INTERACTIONS BETWEEN NMDA-MEDIATED AND PROSTAGLANDIN RECEPTOR-MEDIATED EVENTS IN A MODEL OF INFLAMMATORY NOCICEPTION

Preadministered niflumic acid, a nonsteroidal anti-inflammatory drug ( 1, 3 and 9 mg/kg i.v.), dose-relatedly reduced carrageenan-evoked spin al c-Fos expression and the peripheral ankle oedema, with the highest dose reducing in parallel both parameters (55 +/- 3% reduction of carr ageenan c-Fos expression, 57 +/- 13% reduction of carrageenan-evoked a nkle oedema, respectively, P < 0.001 for both). Co-administration of l ow doses of niflumic acid and (+)-HA966, a low-efficacy partial agonis t at the glycine site of the NMDA receptor (1 mg/kg i.v. + 2.5 mg/kg s .c., respectively) significantly reduced spinal c-Fos expression, this effect was significantly different from the lack of effect of niflumi c acid alone or (+)-HA966 alone on spinal c-Fos expression (P < 0.01 f or both drugs). Co-administered niflumic acid and (+)-HA966 did not in fluence the peripheral carrageenan-evoked oedema. Spinal interactions between prostaglandin- and NMDA receptor-mediated events during inflam matory nociceptive transmission are discussed.