Central noradrenergic mediation of nitrous oxide-induced analgesia in rats.

Abstract

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 still 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. 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 micrograms.kg-1, i.p.), alpha 2 receptor antagonist, idazoxone(IDZ: 100 micrograms.kg-1, i.v.) by lesioning the locus coeruleus (LC) seven days before exposure to N2O, or naloxone (5 mg.kg-1, i.v.). Also, in a NAergic neuronal transmission study, the changes in NA content at LC and spinal cord were determined using HPLC-ECD. Nitrous oxide produced analgesia, % MPE increased to a maximum of 78% at 30 min, thereafter declining to 38% at 120 min. 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. 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.