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PEDIATRIC ANESTHESIA

Nitrous Oxide Lacks the Antinociceptive Effect on the Tail Flick Test in Newborn Rats

Masahiko Fujinaga, MD^*,,, Ryan Doone^*,, M. Frances Davies, PhD^*,, and Mervyn Maze, MB, ChB, FRCP, FRCA^*,,

*Department of Anesthesia, Stanford University School of Medicine, Stanford; Anesthesiology Service, V.A. Palo Alto Health Care System, Palo Alto, California; and Magill Department of Anaesthetics, Chelsea and Westminster Campus, Imperial College of Science, Technology and Medicine, University of London, London, United Kingdom

Address correspondence and reprint requests to Masahiko Fujinaga, MD, Magill Department of Anaesthetics, Chelsea and Westminster Hospital, 369 Fulham Rd., London, SW10 9NH, UK. Address e-mail to m.fujinaga{at}ic.ac.uk

Nitrous oxide (N₂O) is commonly used for pediatric anesthesia under the assumption that it produces a similar analgesic response to that seen in adults. We examined the antinociceptive effect of 75% N₂O on tail flick latency response in newborn rats at postnatal Day 1 (PD 1), PD 8, PD 15, PD 22, and PD 29. Up to PD 15, rats showed no analgesic effect to N₂O. By PD 29, rats exhibited a comparable analgesic effect to that seen in adult animals. These data are consistent with the fact that the descending noradrenergic neurons, which are required for the analgesic action of N₂O, are not anatomically or functionally developed at birth and take more than three weeks to fully develop in rats.

Implications: The present study indicates that rats below 3 wk old lack an antinociceptive effect to nitrous oxide by using the tail flick test. Because a 3-wk-old rat is comparable in neurological development with the toddler stage in humans, we may anticipate that patients below this age may not experience the usual analgesic effect of nitrous oxide.

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