The contribution of NMDA receptor activation to spinal c‐Fos expression in a model of inflammatory pain

Abstract

1 Intraplantar carrageenin (6 mg 150 μ1‐¹) 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 ≤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 mg kg⁻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 ≤ 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≤0.05, for all 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≤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.