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To understand and exploit centrally acting drugs requires reliable measures of their time course of action in the human brain. Functional magnetic resonance imaging (fMRI) is able to measure noninvasively, drug-induced changes in task-related brain activity. Here, we have characterized, in a specific region of the brain, the time of onset of action and the half-life of action of a clinically relevant dose of a potent opioid analgesic agent, remifentanil. These times were established from the temporal variation of the amplitude of the blood oxygen level-dependent response in the insular cortex contralateral to a painfully hot thermal stimulus, in volunteers receiving a remifentanil infusion. The insular cortex has repeatedly been reported as activated by noxious thermal stimulation. The times of onset and offset of drug action were each characterized by a half-life for changes in fMRI signal from within the insula. These characteristic times agreed with the observed drug-induced analgesia and previous pharmacokinetic-pharmacodynamic measurements for remifentanil. We have successfully measured, for the first time using fMRI, temporal pharmacological parameters for a CNS-active drug based on its effect on task-related activity in a specific brain region. Comparison of the time course of regional brain activity with pain perception could reveal those regions engaged in drug-induced analgesia.

Original publication




Journal article



Publication Date





626 - 635


Adult, Analgesics, Opioid, Brain, Confidence Intervals, Humans, Magnetic Resonance Imaging, Male, Pain Measurement, Piperidines, Remifentanil, Time Factors