The suppression of formalin-induced fos expression by different anesthetic agents in the infant rat

Despite the importance of pediatric anesthesiology, the sites and mechanisms of anesthetic action in the neonate are not well described in either human or nonhuman species. This experiment investigated suppression produced by different anesthetic agents of neuronal activity in the lumbar spinal cord of the 3-day-old rat. The expression of the c-fos immediate early gene following formalin injection into the hindpaw was used as a marker for neuronal activity. Pups were anesthetized by one of the following often-used agents: methoxyflurane, acepromazine, a mixture of ketamine and xylazine, and hypothermia. All treatments induced behavioral anesthesia. Despite the behavioral anesthesia, the ketamine-xylazine mixture was completely ineffective in suppressing formalin-induced-Fos expression. In contrast, methoxyflurane and hypothermia blocked the appearance of the Fos protein. Similarly, acepromazine was effective in eliminating some of the Fos-labeled nuclei. These data suggest that, in the infant rat, both hypothermia and methoxyflurane act in part at the spinal level by depressing either primary afferents or dorsal horn neuronal activity whereas the site of action for ketamine-xylazine may be located supraspinally.