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BJA Advance Access originally published online on July 1, 2005
British Journal of Anaesthesia 2005 95(3):393-399; doi:10.1093/bja/aei182
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© The Board of Management and Trustees of the British Journal of Anaesthesia 2005. All rights reserved. For Permissions, please e-mail: journal.permissions@oupjournals.org

Isoflurane exerts antinociceptive and hypnotic properties at all ages in Fischer rats

R. D. Sanders1,2, N. Patel1, M. Hossain1, D. Ma1,* and M. Maze1–3,

1 Department of Anaesthetics and Intensive Care, Faculty of Medicine, Imperial College, London, UK. 2 Magill Department of Anaesthesia, Intensive Care and Pain Management, Chelsea and Westminster Hospital, Chelsea and Westminster Healthcare NHS Trust, London, UK. 3 Biophysics Section, Department of Biological Sciences, Imperial College, London, UK

* Corresponding author. E-mail: d.ma{at}imperial.ac.uk

Background. Some anaesthetic agents exhibit an age-dependent analgesic effect, for example nitrous oxide, which is ineffective in newborn rats. We investigated whether a similar time dependency existed for the responses to the volatile anaesthetic isoflurane.

Methods. The analgesic and hypnotic properties of isoflurane at various ages was assessed using four cohorts of Fischer rats aged approximately 7, 16, and 28 days and adults (11–12 weeks old). Intraplantar administration of formalin mimicked inflammatory pain, and its effects were assessed using immunohistochemical (c-Fos staining) and behavioural paradigms. The hypnotic properties of isoflurane were assessed using loss of righting reflex.

Results. Formalin administration produced a typical nociceptive response observed both behaviourally and immunohistochemically in all age groups; these nociceptive responses were significantly attenuated by isoflurane 0.5% at each age (P<0.05). Interestingly 7-day-old animals showed a significantly more potent hypnotic response than older animals (P<0.01): with adult rats being most resistant to isoflurane induced hypnosis (P<0.05).

Conclusion. In contrast to nitrous oxide, isoflurane is an effective antinociceptive agent in neonatal rats. If the data can be extrapolated to clinical scenarios these results suggest that isoflurane may be analgesic in newborns as well as adult humans. In addition, isoflurane is a potent hypnotic, especially in the very young, which is in contrast to the neonate's relative resistance to anaesthesia as assessed by minimum alveolar concentration.


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R. D. Sanders, D. Ma, P. Brooks, and M. Maze
Balancing paediatric anaesthesia: preclinical insights into analgesia, hypnosis, neuroprotection, and neurotoxicity
Br. J. Anaesth., November 1, 2008; 101(5): 597 - 609.
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