BACKGROUND: Nitrous oxide (N2O) acts on supraspinal noradrenergic neurons to produce analgesia, but it is unclear if analgesia contributes to N2O's immobilizing effects. We tested the hypothesis that N2O minimum alveolar anesthetic concentration (MAC) is unchanged after selective ablation of supraspinal noradrenergic neurons, or in naïve animals at N2O exposure timepoints when analgesia is absent. METHODS: We determined tailflick latency (TFL) and hindpaw withdrawal latency (HPL) under 70% N2O, N2O MAC, and isoflurane MAC before and after intracerebroventricular 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), N2O MAC was determined at 25-45 min after initiation of N2O exposure (during peak analgesia) and again at 120-140 min (after TFL and HPL returned to baseline). RESULTS: After 30 min of N2O exposure, TFL and HPL increased significantly but declined back to baseline within 120 min. N2O did not produce analgesia in rats that received SAP-DBH. However, N2O and isoflurane MAC were not significantly different between SAP-DBH and control-injected animals (Mean ± sd for N2O: 1.7 ± 0.1 atm vs 1.7 ± 0.2 atm; isofurane: 1.6 ± 0.2% vs 1.7 ± 0.2%). In naïve animals, N2O 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 N2O removes its analgesic effects, but does not change MAC. The immobilizing mechanism of N2O is independent from its analgesic effects.
ASJC Scopus subject areas
- Anesthesiology and Pain Medicine