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Neuropsychopharmacology. 2004 Mar;29(3):626-35.

Using fMRI to quantify the time dependence of remifentanil analgesia in the human brain.

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1
Department of Clinical Neurology, Centre for Functional Magnetic Resonance Imaging of the Brain, University of Oxford, John Radcliffe Hospital, Oxford, UK. wise@fmrib.ox.ac.uk

Abstract

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.

PMID:
14679387
DOI:
10.1038/sj.npp.1300364
[Indexed for MEDLINE]
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