Nitrous oxide-induced analgesia does not influence nitrous oxide's immobilizing requirements.

BACKGROUND: Nitrous oxide (N 2 O) acts on supraspinal noradrenergic neurons to produce analgesia, but it is unclear if analgesia contributes to N 2 O's immobilizing effects. We tested the hypothesis that N 2 O minimum alveolar anesthetic concentration (MAC) is unchanged after selective ablation of supraspinal noradrenergic neurons, or in naive animals at N 2 O exposure timepoints when analgesia is absent. METHODS: We determined tailflick latency (TFL) and hindpaw withdrawal latency (HPL) under 70% N 2 O, N 2 O MAC, and isoflurane MAC before and after intrace-rebroventricular injections of anti-dopamine-β hydroxylase conjugated to saporin (SAP-DBH; n = 7), or a control antibody conjugated to saporin (n = 5). In a separate group of naive rats (n = 8), N 2 O MAC was determined at 25-45 min after initiation of N 2 O exposure (during peak analgesia) and again at 120-140 min (after TFL and HPL returned to baseline). RESULTS: After 30 min of N 2 O exposure, TFL and HPL increased significantly but declined back to baseline within 120 min. N 2 O did not produce analgesia in rats that received SAP-DBH. However, N 2 O and isoflurane MAC were not significantly different between SAP-DBH and control-injected animals (Mean ± SD for N 2 O: 1.7 ± 0.1 atm vs 1.7 ± 0.2 atm; isofurane: 1.6 ± 0.2% vs 1.7 ± 0.2%). In naive animals, N 2 O MAC was not different at the 30 min period compared with the 120 min period (1.8 ± 0.1 atm vs 1.8 ± 0.2 atm). CONCLUSIONS: Destroying brainstem noradrenergic neurons or prolonged exposure to N 2 O removes its analgesic effects, but does not change MAC. The immobilizing mechanism of N 2 O is independent from its analgesic effects.