Is Electrical Brain Activity a Reliable Biomarker for Opioid Analgesia in the Gut?

Authors

  • Camilla Staahl,

    1. Mech-Sense, Department of Gastroenterology, Aalborg Hospital, Aarhus University, Aarhus, Denmark
    2. Center for Sensory-Motor Interactions (SMI), Department of Health Science and Technology, Aalborg University, Aalborg, Denmark
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  • Anne L. Krarup,

    1. Mech-Sense, Department of Gastroenterology, Aalborg Hospital, Aarhus University, Aarhus, Denmark
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  • Anne E. Olesen,

    1. Mech-Sense, Department of Gastroenterology, Aalborg Hospital, Aarhus University, Aarhus, Denmark
    2. Center for Sensory-Motor Interactions (SMI), Department of Health Science and Technology, Aalborg University, Aalborg, Denmark
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  • Christina Brock,

    1. Mech-Sense, Department of Gastroenterology, Aalborg Hospital, Aarhus University, Aarhus, Denmark
    2. Center for Sensory-Motor Interactions (SMI), Department of Health Science and Technology, Aalborg University, Aalborg, Denmark
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  • Carina Graversen,

    1. Mech-Sense, Department of Gastroenterology, Aalborg Hospital, Aarhus University, Aarhus, Denmark
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  • Asbjørn M. Drewes

    1. Mech-Sense, Department of Gastroenterology, Aalborg Hospital, Aarhus University, Aarhus, Denmark
    2. Center for Sensory-Motor Interactions (SMI), Department of Health Science and Technology, Aalborg University, Aalborg, Denmark
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Author for correspondence: Camilla Staahl, Grünenthal GmBH, Global Early Clinical Development, Zieglerstrasse 6, D-52078 Aachen, Germany (e-mail camilla.staahl@grunenthal.com).

Abstract

Abstract:  The effects of morphine on brain potentials after experimental gut pain have never been investigated. This study explored whether multi-channel-evoked brain potentials (EP) and corresponding dipole sources in the brain would reflect the effects of morphine on experimental oesophageal pain. In a crossover study, the effects of oral morphine (30 mg) or corresponding placebo on pain from electrical oesophageal stimulation were tested in 12 healthy male volunteers. The electroencephalographic (EEG) activity was monitored with 64 surface recordings. Pain was assessed by subjective scores on a visual analogue scale, amplitude and latency of the vertex-EP as well as on multi-channel recordings of EPs. Finally, electrical brain sources after pain stimuli were modelled from the EEG data. Morphine attenuated subjective pain scores (= 0.008). The amplitude of the P2 peak (230 msec. post-stimulus) in the vertex EPs was unaltered after treatment with morphine, whereas after placebo treatment, it decreased (= 0.03). However, the overall topography changed and the source of P1 (100 msec. post-stimulus), possibly originating from areas near the cingulate gyrus, changed localization in an upward, posterior direction (= 0.04). The length of the vector describing this shift correlated inversely with the magnitude of the subjective pain relief (= −0.7; = 0.02). With the potential of becoming a useful biomarker in analgesic trials, the localization of the dipole sources reflected the analgesic action of morphine after pain stimuli of the gut. Even though further evaluation of the method is necessary, it has the potential to be a valid objective biomarker for opioid analgesia.

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