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


CONCLUSIONS
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.
Department of Anaesthetics and Intensive Care, Faculty of Medicine, Imperial College, London, UK.
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Sanders
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Patel
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Hossain
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Maze
D000375:Aging / Q000502:physiology*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D004305:Dose-Response Relationship, Drug; D005557:Formaldehyde; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D007530:Isoflurane / Q000494:pharmacology*; D008159:Lumbar Vertebrae; D009619:Nociceptors / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012018:Reflex / Q000187:drug effects; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology
D018712:Analgesics, Non-Narcotic; D018685:Anesthetics, Inhalation; D006993:Hypnotics and Sedatives; D016760:Proto-Oncogene Proteins c-fos; D005557:Formaldehyde; D007530:Isoflurane