Central Noradrenergic Mediation of Nitrous Oxide-induced Analgesia in Rats

Because of its potent analgesic action, nitrous oxide(N_2O) has been widely used in clinical practice. Although several studies suggest that N_2O may produce analgesia by interacting with opioid receptors, definite mechamisms are not fully understood yet. The present study was undertaken to examine an involvement of noradrenergic neuronal activity for N_2O-induced analgesia in relation to the alpha-2 receptor function at the spinal and supraspinal levels in rats. Male Wistar rats were used. Analgesia was evaluated by using tail-flick method and expressed as %MPE values. Noradrenaline (NA) content was determined by HPLOECD and alpha-2 receptor binding (3^H-clonidine binding) was evaluated using in vitro autoradiography. N_20 (75%) produced analgesia, the %MPE value being increased to a maximum value of 78% at 30min, thereafter declined gradually to 38% at 120 min after exposure. Alpha-2 agonist clonidine(CLO: 150/μg/kg,ip, given 30 min before N_2O exposure) potentiated analgesic effect of N_2O at 120 min (%MPE: 80%), while alpha-2 receptor antagonist idazoxane (100μg/kg,ip) or locus coeruleus (LC) lesions (produced 7 days prior to N_2O exposure) attenuated analgesic effect of N_2O. Naloxone(5mg/kg,iv) in a dose that blocks analgesic effect of morphine (5mg/kg) did not affect N_2O-induced analgesia. 3^H-CLO hinding site in laminae 1-ll in the dorsal horm of the spinal cord was increased by 16% with N_2O. In the LC, NA content was decreased by 52% and 3^H-CLO binding site was increased by 13%. With morphine, 3^H-CLO binding sites were increased by 13% and 20% in the LC and periaqueductal gray, respectively. The results suggest that N_2O produces analgesia by interacting with central noradrenergic systems via the alpha-2 receptor activation and hence activating of the descending inhibitory system.

笑気鎮痛

ノルアドレナリン神経系

下行性抑制系

α_2受容体

インビトロオートラジオフラフィー