British Journal of Anaesthesia, Vol 76, Issue 1 99-105, Copyright © 1996 by The Board of Management and Trustees of the British Journal of Anaesthesia
W. Z. Sun, B. C. Shyu and J. Y. Shieh
In rats injected s.c. with formalin, behavioural correlates of the amount
and pattern of Fos-like immunoreactivity (Fos-Ll) (molecular responses to
pain) were studied to test if early phase treatment with 75% nitrous oxide
or 2% halothane, or both, suppressed subsequent spinal sensitization. Rats
were allocated to four treatment groups: (1) 100% oxygen (control, n = 15),
(2) 75% nitrous oxide (0.5 MAC, n = 12), (3) 2% halothane (1 MAC, n = 12),
and (4) 75% nitrous oxide with 2% halothane (1.5 MAC, n = 18) for 20 min.
Each rat then received a s.c. injection of 1% formalin 50 microliters into
the left hindpaw and anaesthesia was maintained for another 5 min (early
phase). A fifth group of rats receiving fentanyl 100 micrograms kg-1 (n =
12) 10 min before formalin injection were studied simultaneously as a
positive control. Rats in all groups were killed 60 min after formalin
injection and maximal counts of Fos-Ll labelled neurones in the dorsal horn
of the rat spinal cord were compared according to laminar distribution.
Formalin-induced behavioural hyperalgesia during the early phase was
suppressed completely by fentanyl, 75% nitrous oxide, or 2% halothane, or
both. The late phase response was attenuated by all four anaesthetic
regimens within 20 min after injection, whereas behavioural scores for the
nitrous oxide, halothane, or both, groups were nearly identical to the
control 20 min later. Fentanyl suppressed the late phase response until 30
min after formalin injection but failed to reduce it thereafter. The
numbers of Fos-Ll labelled neurones for groups given nitrous oxide, or
halothane, or both, were identical to the control, whereas numbers for
fentanyl were 47.2% less (P < 0.01). The decrease occurred predominantly
in the neck of the dorsal horn (44.9% of control, P < 0.01) and also in
the nucleus proprius and superficial laminae (54.4% and 56.2% of control, P
< 0.05). In summary, we found that nitrous oxide, or halothane, or both,
did not suppress subsequent spinal sensitization to noxious stimulation.
This result supports the previous hypothesis that inhalation anaesthesia
lacks pre-emptive analgesic action. Inhalation anaesthetic agents, unlike
fentanyl, suppress the early and late phase response because of anaesthetic
but not analgesic effects. Thus, we suggest that measuring the genetic
product of c-fos proto-oncogene is a useful adjunct to pharmacological
tests whenever behavioural hyperalgesia is questionable or unobtainable.
LABORATORY INVESTIGATIONS
Nitrous oxide or halothane, or both, fail to suppress c-fos expression in rat spinal cord dorsal horn neurones after subcutaneous formalin
Department of Anaesthesiology, Medical College of National Taiwan University, Taipei, Taiwan; Department of Anatomy, Medical College of National Taiwan University, Taipei, Taiwan; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
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