Background. Previous studies have suggested that focal cryogenic brain
lesions that cause functional cerebral depression may increase anesth
etic potency. To determine whether this effect was caused by changes i
n nociception, this study prospectively evaluated the influence of an
experimental focal brain injury on the analgesic effects of the opioid
s, fentanyl and alfentanil, in rats. Methods: The cortical freezing le
sion was made with a brass probe cooled to -50-degrees-C, applied thro
ugh a craniotomy to the intact dura for 5 s. The analgesic effects of
the opioids were quantified by tail-flick latency 3 days after the inj
ury. The prolongation of tail-flick latency by infusions of each opioi
d in animals injured with a standardized cortical freezing lesion was
compared with the results obtained from sham-operated control animals.
Results. At the endpoint of the experiment, prolongation of the tail-
flick latency to 10 s, the mean serum concentrations (EC50) of both fe
ntanyl and alfentanil were approximately 25% less in the brain-injured
animals than in the controls (EC50 fentanyl; injured: 10.2 +/- 2.6 ng
/ml, controls: 13.6 +/- 5.2 ng/ml [P < 0.02]; EC50 alfentanil; injured
: 54.7 +/- 9.2 ng/ml, controls: 74.3 +/- 18.4 ng/ml [P < 0.02]). For a
lfentanil, no significant differences in pharmacokinetics between inju
red and control animals were observed. Conclusions. These results supp
ort the hypothesis that reductions in anesthetic requirements in this
animal model of brain injury may be caused, in part, by alterations in
nociception.