title: Using fMRI to quantify the time dependence of remifentanil analgesia in the human brain.
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.
authors.affiliation: 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
authors.forename: Richard G
authors.initials: RG
authors.lastname: Wise
authors.forename: Pauline
authors.initials: P
authors.lastname: Williams
authors.forename: Irene
authors.initials: I
authors.lastname: Tracey
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D016001:Confidence Intervals; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D010880:Piperidines / Q000494:pharmacology*; D000077208:Remifentanil; D013997:Time Factors
chemical_list: D000701:Analgesics, Opioid; D010880:Piperidines; D000077208:Remifentanil