BACKGROUND: Pretreatment of systemic ketamine reduced pain behaviors in some animal models with persistent pain. However, a clinically relevant preemptive analgeisic effect of systemic ketamine is controversial. The purpose of this study was to examine the preemptive effect of systemic ketamine in rats undergoing a plantar incision. METHODS: Ketamine (10, 30, or 100 mg/kg) or a saline vehicle was administered subcutaneously 30 minutes before an incision was made. Withdrawal thresholds to calibrated von Frey filaments adjacent to the wound were measured before incision and from 2 hours to postoperative 6 days after incision. To evaluate the effectiveness of an extension of antinociceptive treatment into the initial postoperative period, 30 mg/kg ketamine or a saline vehicle 30 minutes before an incision was made was administered subcutaneously followed by injection of 5 more of the same drug or vehicle every 1 hour. The development of pain behavior was also evaluated before incision and from 30 minutes after last drug injection to postoperative 6 days. RESULTS: In saline vehicle-treated rats, mechanical hyperalgesia was persistent through day 1 after surgery and then gradually returned to the preincisional value. Thirty mg/kg ketamine increased the withdrawal threshold at 2 hours. One hundred mg/kg ketamine caused a motor block at 2 hours and increased the withdrawal threshold at 2.5 and 3 hours. A repeated injection of 30 mg/kg ketamine caused a motor block during the first 2 hours, and reduced hyperalgesia at 3 and 4 hours after the last drug injection. However, there were no significant differences in withdrawal thresholds among the groups at all subsequent times. CONCLUSIONS: Antinociceptive treatment of systemic ketamine covers the period of surgery and the initial postoperative period by reducing early pain behavior, but had no impact on subsequent measures of hyperalgesia. Therefore, a preemptive effect of systemic ketamine in postoperative pain seems unlikely.