The contribution of NMDA receptor activation to spinal c-Fos expression in a model of inflammatory pain.
1. Intraplantar carrageenin (6 mg 150 microliters-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 < or = 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 afterintraplantar 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 tocontrol 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.
Chapman
V
V
Physiopharmacologie du Système Nerveux, INSERM U.161 and EPHE, Paris, France.
Honoré
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P
Buritova
J
J
Besson
J M
JM
D000818:Animals; D002351:Carrageenan / Q000633:toxicity; D004195:Disease Models, Animal; D004347:Drug Interactions; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D008297:Male; D009187:Myelitis / Q000139:chemically induced / Q000150:complications / Q000378:metabolism*; D010146:Pain / Q000503:physiopathology*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D013997:Time Factors
D016760:Proto-Oncogene Proteins c-fos; D011760:Pyrrolidinones; D016194:Receptors, N-Methyl-D-Aspartate; D002351:Carrageenan; C001369:1-hydroxy-3-amino-2-pyrrolidone