Central noradrenergic mediation of nitrous oxide-induced analgesia in rats

Purpose: Although several studies have demonstrated that both supra opiate receptors and spinal alpha(2) adrenoceptors play a mediating role in nitrous oxide(N2O) analgesia, controversy stilt exists. The present study was undertaken to evaluate further the involvement of noradrenergic (NA) neuronal activity in N2O analgesia by investigating tail-flick latency and supra-and spinal NA levels in rats: Methods: In an analgesia study, effect of N2O 75% and its modification were evaluated using the tail-flick test in male Wistar rats; Results were expressed as % maximum possible effect (MPE). Modification of N2O analgesia was examined in rats pretreated with either the alpha(2) receptor agonist, clonidine(CLO: 150 mu g.kg(-1), ip), alpha(2) receptor antagonist, idazoxone(IDZ: 100 mu g.kg(-1) iv) by lesioning the locus coeruleus (LC) seven days before exposure to N2O, or naloxone (5mg.kg(-1), iv). Also, in a NAergic neuronal transmission study, the changes in NA content at Le and spinal cord were determined using HPLC-ECD, Results: Nitrous oxide produced analgesia, % MPE increased to a maximum of 78% at 30min, thereafter declining to 38% at 120min. Clonidine potentiated the analgesic effect of N2O at 120 min (80%). The analgesic effect of N2O was attenuated by IDZ or by LC lesioning, However, naloxone, in a dose sufficient to block morphine-induced analgesia, had no effect. With N2O exposure, NA content was decreased by 52% in the LC and by 20% at spinal cord, With morphine, NA content did not differ from the control group. Conclusion: The data suggest that N2O-induced analgesia is principally mediated by activation of the descending inhibitory NAergic system and/or Increased NA release at spinal cord which may lead to presynaptic inhibition of primary afferent neurotransmitter release and hyperpolarize the dorsal horn neurons by alpha(2) receptors.