Concomitant administration of morphine and an N-methyl-D-aspartate receptor antagonist profoundly reduces inflammatory evoked spinal c-Fos expression.
BACKGROUND
After intraplantar injection of carrageenin, peripheral inflammation and spinal c-Fos expression are extensive, with the latter being sensitive to both large doses of morphine or N-methyl-D-aspartate receptor antagonism. The authors investigated the effects of coadministered morphine and (+)-HA966, a functional antagonist at the glycine site of the N-methyl-D-aspartate receptor, on the two parameters.


METHODS
The effects of morphine, (+)-HA966 and coadministration of morphine and (+)-HA966 on spinal c-Fos expression in segments L4-L5 of the spinal cord and peripheral edema, induced at 1.5 h and 3 h after intraplantar carrageenin (6 mg/150 microliters) were studied.


RESULTS
Previous coadministration of 0.3 mg/kg systemic morphine and 2.5 mg/kg subcutaneous (+)-HA966 significantly reduced c-Fos expression induced 1.5 h, but not 3 h, after carrageenin administration. However, coadministration of a larger dose of morphine (3 mg/kg) with (+)-HA966 (2.5 mg/kg) reduced c-Fos expression at 3 h after carrageenin administration, in a partially naloxone-reversible manner.


CONCLUSIONS
Concurrent mu-opioid receptor activation and N-methyl-D-aspartate receptor antagonism reduces nociceptive transmission at the level of the spinal cord, as shown by the reduction of carrageenin-evoked c-Fos expression.
Honoré
P
P
Institut National de la Santé et de la Recherche Médicale, Paris, France.
Chapman
V
V
Buritova
J
J
Besson
J M
JM
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002351:Carrageenan / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D016762:Genes, fos / Q000187:drug effects*; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D017450:Receptors, Opioid, mu / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism
D000701:Analgesics, Opioid; D011760:Pyrrolidinones; D016194:Receptors, N-Methyl-D-Aspartate; D017450:Receptors, Opioid, mu; D009020:Morphine; D002351:Carrageenan; C001369:1-hydroxy-3-amino-2-pyrrolidone