EFFECT OF SYSTEMIC N-METHYL-D-ASPARTATE RECEPTOR ANTAGONIST (KETAMINE) ON PRIMARY AND SECONDARY HYPERALGESIA IN HUMANS

Ketamine reduces nociception by binding noncompetitively to the N-meth yl-D-aspartate (NMDA) receptor, activation of which increases spinal h ypersensitivity. We studied 19 healthy, unmedicated male volunteers, a ged 20-31 yr. Burn injuries were produced on the medial surface of the dominant calf with a 25 x 50 mm rectangular thermode. On 3 separate d ays, at least 1 week apart, subjects received a bolus of either ketami ne 0.15 mg kg(-1), ketamine 0.30 mg kg(-1) or placebo, delivered by a mechanical infusion pump over 15 min. The bolus was followed by contin uous infusion of ketamine 0.15 mg kg(-1) h(-1), ketamine 0.30 mg kg(-1 ) h(-1) or placebo, respectively, for 135 min. Ketamine reduced the ma gnitude of both primary and secondary hyperalgesia, and also pain evok ed by prolonged noxious heat stimulation, in a dose-dependent manner. In contrast, ketamine did not alter phasic heat pain perception (perce ption of transient, painful, thermal stimuli) in undamaged skin. The a nalgesic effects of ketamine in the burn injury model are in agreement with results from experimental studies, and can be distinguished from those of local anaesthetics and opioids. Side effects caused by conti nuous infusion of ketamine 0.15 and 0.30 mg kg(-1) h(-1) were frequent but clinically acceptable.