THE INFLUENCE OF CRYOGENIC BRAIN INJURY ON NOCICEPTION IN THE RAT

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.