Simultaneous brain, brainstem and spinal cord pharmacological-fMRI reveals involvement of an endogenous opioid network in attentional analgesia

Oliva, Valeria, Hartley-Davies, Ron, Moran, Rosalyn, Pickering, Anthony E. and Brooks, Jonathan C. W. ORCID: (2022) Simultaneous brain, brainstem and spinal cord pharmacological-fMRI reveals involvement of an endogenous opioid network in attentional analgesia. eLife, 11. ISSN 2050-084X

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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.

Item Type: Article
Additional Information: Source 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: and the brainstem regional masks of PAG, LC, RVM are available from Funding Information: The authors would like to thank Aileen Wilson (Lead Research Radiographer, CRiCBristol) for her support in running experiments, and the subjects who kindly agreed to take part. This research was funded in whole, or in part, by the Wellcome Trust [203963/Z/16/Z; and 088373/Z/09/A] and Medical Research Council [MR/N026969/1]. For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.
Uncontrolled Keywords: neuroscience(all),biochemistry, genetics and molecular biology(all),immunology and microbiology(all) ,/dk/atira/pure/subjectarea/asjc/2800
Faculty \ School: Faculty of Social Sciences > School of Psychology
Related URLs:
Depositing User: LivePure Connector
Date Deposited: 03 Feb 2022 12:30
Last Modified: 23 Oct 2022 03:30
DOI: 10.7554/eLife.71877


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