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

Abstract

1 Intraplantar carrageenin (6 mg 150 pi-') 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-' and 2.5 mg kg-', 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-') 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-'), 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-' (+)-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' 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, PS0.05, for all areas). 8 A single post-administration of (+)-HA966 (10 mg kg-'), 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 pre...

The antinociceptive effect of combined systemic administration of morphine and the glycine/NMDA receptor antagonist, (+)‐HA966 in a rat model of peripheral neuropathy

“…(+)-HA966 was dissolved in saline and administered s.c. in a volume of 1 ml kg 71 20 min before morphine. The dose, 2.5 mg kg 71 of (+)-HA966 , was chosen since given alone it produced no antinociceptive e ect in a study on in¯ammatory pain in the rat (Chapman et al, 1995). In each group, the control rats received the same volume of i.v.…”

Bee Venom Pretreatment Has Both an Antinociceptive and Anti-Inflammatory Effect on Carrageenan-Induced Inflammation.

“…Numerous studies have utilized spinal cord Fos expression to evaluate the effectiveness of anti-inflammatory drugs and analgesics in CR-induced hyperalgesia/inflammation [16,31]. Both CRinduced hyperalgesia and spinal Fos expression have been shown to be reduced by systemic administration of opioid [17], NMDA antagonists [4] and nonsteroidal anti-inflammatory drugs (NSAIDs) [16]. Based on these data, CRinduced hyperalgesia/inflammation in rodents has been widely accepted as an appropriate model in which to test the efficacy of anti-inflammatory and/or analgesic drugs.…”

Effects of a partial agonist and a full antagonist acting at the glycine site of the NMDA receptor on inflammation‐induced mechanical hyperalgesia in rats

“…NMDA/glycine site antagonists reverse the enhanced neuronal responses seen after u.v.-induced inflammation (Chapman & Dickensen, 1994), and reverse thermal hyperalgesia evoked by inflammation or peripheral neuropathy in behavioural experiments (Mao et al, 1992;Ren et al, 1992b). Furthermore, the NMDA/glycine site partial agonist, (+ )-HA-966, inhibits spinal c-fos expression in the spinal dorsal horn after intraplantar carrageenin in rats (Chapman et al, 1995). However, to our knowledge, there are no published results on the effects of NMDA/glycine modulatory site antagonists on mechanical hyperalgesia.…”