Advanced Pharmaco-EEG Reveals Morphine Induced Changes in the Brainʼs Pain Network

INTRODUCTION:By using a novel brain source modeling approach, where the evoked potential (EP) signal was decomposed with multichannel matching pursuit (MMP) before source localization, we investigated brain generators of EPs after a pain stimulus in the esophagus before and after administration of placebo/morphine. We showed that this new approach of pharmaco-electroencephalogram (EEG) analysis can shed light on subtle changes, which cannot be foreseen from conventional analysis (amplitude/latency/topography). METHODS:In this placebo-controlled crossover study, the effects of orally administered morphine (30 mg) on esophageal pain elicited by electrical stimulation were investigated in 9 healthy volunteers. Using new methods (decomposition of the EPs with MMP and clustering) in combination with inverse modeling, we investigated brain sources of the EPs and their time–frequency properties. RESULTS:Morphine treatment resulted in a shift of the brain sources in the low-frequency range (2–4 Hz) toward the frontal cortex during the first 300 milliseconds after stimulus, whereas active brain sources after placebo treatment remained stable. CONCLUSIONS:Decomposing the EPs into the original brain generators showed that morphine mainly changes the low frequency electrical activity in the frontal brain area. This method can be used to increase the basic understanding of the opioid effect on the brainʼs processing of pain and eventually identify biomarkers of analgesia in experimental pain models.