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 anesthetic potency. To determine whether this effect was caused by changes in nociception, this study prospectively evaluated the influence of an experimental focal brain injury on the analgesic effects of the opioids, fentanyl and alfentanil, in rats. Methods: The cortical freezing lesion was made with a brass probe cooled to -50-degrees-C, applied through 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 injury. The prolongation of tail-flick latency by infusions of each opioid 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 fentanyl 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 alfentanil, no significant differences in pharmacokinetics between injured and control animals were observed. Conclusions. These results support the hypothesis that reductions in anesthetic requirements in this animal model of brain injury may be caused, in part, by alterations in nociception.