BACKGROUND: The mechanical hyperalgesia that follows peripheral tissue injury results from peripheral and central sensitization. Central sensitization is initiated and maintained by windup that can be prevented by N-methyl-D-aspartate (NMDA) antagonists. NMDA antagonists, therefore, have the potential to prevent and treat pain, although clinical uses are limited because of their side effects. This study was designed to evaluate the analgesic action of intrathecal (IT) magnesium sulphate in a rat model of postoperative pain and investigate the analgesic mechanism of magnesium. METHODS: Forty-two Sprague-Dawley rats (300 +/- 20 g) were prepared with a chronic IT catheter. Under brief enflurane anesthesia, a 1-cm incision including skin, muscle and fascia was made in the plantar aspect of the hind paw and closed. Normal saline, magnesium (30, 100, 300, 600 microgram), NMDA 50 ng or NMDA 50 ng with magnesium 300 microgram was administered via the IT catheter after recovery. Response frequency, using Von Frey filaments, cumulative pain scores and motor deficits were assessed. RESULTS: The mechanical hyperalgesia and nonevoked pain behaviors decreased significantly at 1 h or 1 h and 3 h after IT injection of magnesium 100 microgram or 300 microgram compared to the saline group without profound motor deficits in a rat model of postoperative pain. However, the rats administered with magnesium 600 microgram were lethargic due to severe motor weakness. Effective duration of magnesium decreased significantly in the group of NMDA 50 ng with magnesium 300 microgram compared to that of magnesium 300 microgram administered alone, but the initial effects were similar between the two groups. CONCLUSIONS: We conclude that IT magnesium sulphate can modulate nociceptive processing after tissue injury and the analgesic mechanism of magnesium is involved in NMDA receptors. Magnesium,therefore, may offer a therapeutic agent for postoperative pain and may be an agent that prevents postoperative pain from changing to persistent pathological pain.