Simultaneous brain, brainstem and spinal cord pharmacological-fMRI reveals involvement of an endogenous opioid network in attentional analgesia
- University of California, San Diego, United States
- University of Bristol, United Kingdom
- King's College London, United Kingdom
- University of East Anglia, United Kingdom
Abstract
Pain perception is decreased by shifting attentional focus away from a threatening event. This attentional analgesia engages parallel descending control pathways from anterior cingulate (ACC) to locus coeruleus, and ACC to periaqueductal grey (PAG) - rostral ventromedial medulla (RVM), indicating possible roles for noradrenergic or opioidergic neuromodulators. To determine which pathway modulates nociceptive activity in humans we used simultaneous whole brain-spinal cord pharmacological-fMRI (N=39) across three sessions. Noxious thermal forearm stimulation generated somatotopic-activation of dorsal horn (DH) whose activity correlated with pain report and mirrored attentional pain modulation. Activity in an adjacent cluster reported the interaction between task and noxious stimulus. Effective connectivity analysis revealed that ACC interacts with PAG and RVM to modulate spinal cord activity. Blocking endogenous opioids with Naltrexone impairs attentional analgesia and disrupts RVM-spinal and ACC-PAG connectivity. Noradrenergic augmentation with Reboxetine did not alter attentional analgesia. Cognitive pain modulation involves opioidergic ACC-PAG-RVM descending control which suppresses spinal nociceptive activity.
Data availability
ource data is provided for Figure 2 (A, C, D, E, and supplementary 1, 2 and 3) and Figure 4 (B) and Figure 5. Un-thresholded statistical maps have been shared in Open Science Framework and are available at the following link: https://osf.io/dtpr6/ and the brainstem regional masks of PAG, LC, RVM are available from https://osf.io/xqvb6/
Article and author information
Author details
Anthony E Pickering
Jonathan CW Brooks
Funding
Wellcome Trust (203963/Z/16/Z)
- Valeria Oliva
Wellcome Trust (088373/Z/09/A)
- Anthony E Pickering
Medical Research Council
- Jonathan CW Brooks
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: The study was approved by the University of Bristol Faculty of Science Human Research Ethics Committee (reference 23111759828). All participants were given a participant information sheet. In the first screening/calibration visit, the participants were briefed on the experiment and gave written informed consent.
Copyright
© 2022, Oliva et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Simultaneous brain, brainstem and spinal cord pharmacological-fMRI reveals involvement of an endogenous opioid network in attentional analgesia
eLife 11:e71877.
https://doi.org/10.7554/eLife.71877
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