Fig. 1. For prevention of pathologic pain after severe tissue injury, ketamine administration should cover the entire duration of high-intensity noxious and inflammatory stimulation, not simply the initial trauma. N -methyl-d-aspartate receptors should be blocked during ongoing intraoperative as well as postoperative transmission of nociceptive impulses. Postoperative mobilization may elicit delayed waves of afferent painful stimuli. Regarding acute opiate tolerance-related phenomena, it is as yet unclear whether ketamine is best administered before first use of opioids.