1 Intraplantar carrageenin (6 mg 150 mu l(-1)) evoked a high level of spinal c-Fos expression in the dorsal horn, of segments L4-L5 of the spinal cord, and an extensive peripheral oedema; both parameters were assessed 3 h after carrageenin. 2 Two series of experiments were performed, with the mean total number of Fos like-immunoreactive neurones (Fos-LI), after carrageenin, not being significantly different for the two series of experiments (266 +/- 17 and 332 +/- 31 Fos-LI neurones). For both series of experiments Fos-LI neurones were predominantly located in the superficial and deep laminae, only 10% of the total number of Fos-LI neurones were located in the nucleus proprius and 10% were located in the ventral horn. 3 Pre-administration of the N-methyl-D-aspartate (NMDA) receptor antagonist, (+)-HA966 (0.5 mg kg(-1) and 2.5 mg kg(-1), s.c.), 30 min before carrageenin, did not significantly influence the total number of Fos-LI neurones, as compared to control carrageenin expression. 4 Pre-administration of the highest dose of (+)-HA966 (10 mg kg(-1)) significantly reduced the number of deep laminae Fos-LI neurones (28 +/- 3% reduction of control number of Fos-LI neurones after carrageenin, P less than or equal to 0.05), without influencing the number of superficial Fos-LI neurones. There was a tendency towards a reduction of the number of Fos-LI neurones in the nucleus proprius by the highest concentration of pre-administered (+)-HA966, (31 +/- 8% reduction), but this effect did not reach significance. 5 Pre-plus post-administered (+)-HA966 (0.5 mgkg(-1)), 30 min before and again 45 min after intraplantar carrageenin, did not significantly influence the total number of Fos-LI neurones, as compared to control carrageenin expression. 6 Pre- plus post-administration of 2.5 mg kg(-1) (+)-HA966 significantly reduced the total number of Fos-LI neurones, as compared to control carrageenin expression. This effect was reflected by a significant reduction in the number of Fos-LI neurones in the nucleus proprius (36 +/- 7% reduction of control carrageenin c-Fos expression respectively, P less than or equal to 0.05). 7 Pre-plus post-administration of 10 mg kg(-1) of(+)-HA966 significantly reduced the number of Fos-LI neurones in the superficial laminae, nucleus proprius, deep laminae and ventral horn (33 +/- 0.5%, 55 +/- 6%, 40 +/- 4% and 51 +/- 4% reduction of control carrageenin c-Fos expression, respectively, P less than or equal to 0.05, for ail areas). 8 A single post-administration of (+)-HA966 (10 mg kg(-1)), 45 min after intraplantar carrageenin, did not significantly influence the number of Fos-LI neurones in the superficial, deep laminae or ventral horn, but significantly reduced the number of Fos-LI neurones in the nucleus proprius, as compared to control carrageenin expression (39 +/- 8% reduction of control carrageenin c-Fos expression, P less than or equal to 0.05). 9 None of the concentrations of (+)-HA966 studied, irrespective of the timing of administration, influenced the peripheral carrageenin oedema. Our results illustrate a contribution of central NMDA receptor activation to carrageenin-evoked spinal c-Fos expression. These results extend previous studies demonstrating the contribution of the NMDA receptor to central hyperalgesia and the expression of c-Fos.
