title: Nitrous oxide-induced analgesia does not influence nitrous oxide's immobilizing requirements.
abstract: 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 naïve 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 intracerebroventricular injections of anti-dopamine-beta 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 naïve 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.
authors.affiliation: Department of Anesthesiology and Pain Medicine, University of California School of Medicine, Davis, CA 95616, USA. sljinks@ucdavis.edu
authors.forename: Steven L
authors.initials: SL
authors.lastname: Jinks
authors.forename: Earl
authors.initials: E
authors.lastname: Carstens
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Antognini
mesh_terms: D000320:Adrenergic Fibers / Q000187:drug effects* / Q000201:enzymology; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D007103:Immobilization; D000922:Immunotoxins / Q000008:administration & dosage; D007276:Injections, Intraventricular; D007530:Isoflurane / Q000494:pharmacology; D008297:Male; D009609:Nitrous Oxide / Q000494:pharmacology*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D054789:Ribosome Inactivating Proteins, Type 1 / Q000008:administration & dosage; D000076985:Saporins; D013563:Sympathectomy, Chemical / Q000379:methods; D013997:Time Factors
chemical_list: D018712:Analgesics, Non-Narcotic; D018685:Anesthetics, Inhalation; D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D054789:Ribosome Inactivating Proteins, Type 1; C101397:anti-dopamine beta-hydroxylase immunotoxin; D007530:Isoflurane; D000076985:Saporins; D009609:Nitrous Oxide