An Investigation to Dissociate the Analgesic and Anesthetic Properties of Ketamine Using Functional Magnetic Resonance Imaging

Abstract

Background: Anatomic sites within the brain, which activate in response to noxious stimuli, can be identified with the use of functional magnetic resonance imaging. The aim of this study was to determine whether the analgesic effects of ketamine could be imaged. Methods: Ketamine was administered to eight healthy volunteers with use of a target-controlled infusion to three predicted plasma concentrations: 0 (saline), 50 (subanalgesic), and 200 ng/ml (analgesic, subanesthetic). Volunteers received noxious thermal stimuli and auditory stimuli and performed a motor task within a 3-T human brain imaging magnet. Activation of brain regions in response to noxious and auditory stimuli and during the motor task was compared with behavioral measures. Results: The analgesic subanesthetic dose of ketamine significantly reduced the pain scores, and this matched a decrease in activity within brain regions that activate in response to noxious stimuli, in particular, the insular cortex and thalamus. A different pattern of activation was observed in response to an auditory task. In comparison, smaller behavioral and imaging changes were found for the motor paradigm. The lower dose of ketamine gave similar but smaller nonsignificant effects. Conclusion: The analgesic effect can be measured within a more global effect of ketamine as shown by auditory and motor tasks, and the analgesia produced by ketamine occurs with a smaller degree of cortical processing in pain-related regions.