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

Neuropsychopharmacology. 2004 Mar;29(3):626-35. doi: 10.1038/sj.npp.1300364.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analgesics, Opioid / pharmacology*
  • Brain / drug effects*
  • Brain / metabolism*
  • Confidence Intervals
  • Humans
  • Magnetic Resonance Imaging / methods*
  • Male
  • Pain Measurement / drug effects
  • Pain Measurement / methods
  • Piperidines / pharmacology*
  • Remifentanil
  • Time Factors


  • Analgesics, Opioid
  • Piperidines
  • Remifentanil