N-methyl-D-aspartate receptors are implicated in hyperresponsiveness following naloxone reversal of alfentanil in isolated rat spinal cord.
In isolated neonatal rat spinal cord, naloxone administered after an opioid increases a nociceptive-related slow ventral root potential (sVRP) to levels above pre-drug controls. We studied the role of N-methyl-D-aspartate (NMDA) receptors in this phenomenon, which may be related to acute tolerance and to hyperalgesia on antagonist-precipitated withdrawal. Naloxone (200 nM) alone produced no significant effect on sVRP area, while naloxone (560 nM) increased area to 121 +/- 17.7% of control (mean +/- SD). Following 200 nM alfentanil, naloxone (200 nM) was associated with a significant rebound in sVRP area to 138 +/- 18.0% of pre-drug control. Hyperresponsiveness developed within 7 min of initial alfentanil exposure. The non-competitive NMDA antagonist MK-801 (20 nM) had no effect on sVRP area when applied alone; higher concentrations produced irreversible depression. MK-801 (20 nM) co-applied with 200 nM alfentanil blocked the rebound increase in sVRP area following naloxone 200 nM and also the increase following naloxone alone (560 nM). The results suggest that alfentanil induces a rapid NMDA receptor-dependent change in spinal cord neuronal excitability.
Feng
J
J
Department of Anesthesia, Stanford University School of Medicine, CA 94305, USA.
Kendig
J J
JJ
D015760:Alfentanil / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D005071:Evoked Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D009270:Naloxone / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects*
D016194:Receptors, N-Methyl-D-Aspartate; D015760:Alfentanil; D009270:Naloxone; D016291:Dizocilpine Maleate