Preemptive analgesia is based on administration of an analgesic before a painful stimulus generates, so as to prevent the subsequent rebound mechanism. Tissue injury results in disruption of the processing mechanisms of noxious stimuli afferent to the CNS (central nervous system) by way of an increase of inputs in the spinal cord. These reactions may be reduced by the administration of opioids. Few studies on preemptive analgesia with opioids in children are available, and none of them is concerned with pediatric neurosurgery. Tramadol and fentanyl are synthetic opioids which are relatively new and act through the activation of pain-inhibitory mechanisms. We conducted a randomized, prospective trial on the preemptive effects in children of these two analgesic drugs, administered according to three different protocols: tramadol as a bolus (1 mg/kg); tramadol by continuous infusion (150 microg/kg per h); fentanyl by continuous infusion (2 microg/kg per h). In all, 42 children undergoing major neurosurgical operations were enrolled in the study, 14 in each treatment group. Each treatment was started at the induction of general anesthesia and continued throughout the entire duration of the operation. The postoperative pain evaluation was conducted in the Pediatric Intensive Care Unit at the end of the surgical operations and involved comparison of any changes in behavioral (AFS scale and CHEOPS score) and hemodynamic (heart rate, respiratory rate, systolic and diastolic arterial pressure, oxygen saturation, O(2) and CO(2) partial pressure) parameters. Only 2 children, both in group A, needed further drug administration postoperatively. No significant side effects were noticed in any of the three groups, except that in group A there was a higher incidence of nausea and vomiting. Tramadol efficacy seems to be better when it is administered in continuous infusion; this treatment modality also leads to fewer adverse effects. Fentanyl, in contrast, proved to be superior to tramadol in the treatment of postoperative pain. In conclusion, preemptive analgesia is a valid technique for the treatment of acute pain in children undergoing major neurosurgical operations.