The association between pain-induced autonomic reactivity and descending pain control is mediated by the periaqueductal grey.
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Authors
Makovac, Elena
Venezia, Alessandra
Hohenschurz-Schmidt, David
Dipasquale, Ottavia
Jackson, Jade B
Medina, Sonia
O'Daly, Owen
Williams, Steve Cr
McMahon, Stephen B
Howard, Matthew A
Publication Date
2021-10-13Journal Title
The Journal of Physiology
ISSN
0022-3751
Publisher
Wiley
Language
eng
Type
Article
This Version
VoR
Metadata
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Makovac, E., Venezia, A., Hohenschurz-Schmidt, D., Dipasquale, O., Jackson, J. B., Medina, S., O'Daly, O., et al. (2021). The association between pain-induced autonomic reactivity and descending pain control is mediated by the periaqueductal grey.. The Journal of Physiology https://doi.org/10.1113/JP282013
Abstract
There is a strict interaction between the autonomic nervous system (ANS) and pain, which might involve descending pain modulatory mechanisms. The periaqueductal grey (PAG) is involved both in descending pain modulation and ANS, but its role in mediating this relationship has not yet been explored. Here, we sought to determine brain regions mediating ANS and descending pain control associations. Thirty participants underwent conditioned pain modulation (CPM) assessments, in which they rated painful pressure stimuli applied to their thumbnail, either alone or with a painful cold contralateral stimulation. Differences in pain ratings between ‘pressure-only’ and ‘pressure + cold’ stimuli provided a measure of descending pain control. In 18 of the 30 participants, structural scans and two functional MRI assessments, one pain-free and one during cold-pain were acquired. Heart rate variability (HRV) was simultaneously recorded. Normalised low-frequency HRV (LF-HRVnu) and the CPM score were negatively correlated; individuals with higher LF-HRVnu during pain reported reductions in pain during CPM. PAG-ventro-medial prefrontal cortex (vmPFC) and PAG-rostral ventromedial medulla (RVM) functional connectivity correlated negatively with the CPM. Importantly, PAG-vmPFC functional connectivity mediated the strength of the LF-HRVnu-CPM association. CPM response magnitude was also negatively correlated with vmPFC GM volume. Our multi-modal approach, using behavioural, physiological and MRI measures, provides important new evidence of interactions between ANS and descending pain mechanisms. ANS dysregulation and dysfunctional descending pain modulation are characteristics of chronic pain. We suggest that further investigation of body-brain interactions in chronic pain patients may catalyse the development of new treatments.
Keywords
descending pain modulation, heart rate variability, periaqueductal grey, resting state, voxel-based morphometry
Sponsorship
Medical Research Council (MC_UU_00005/17)
Identifiers
External DOI: https://doi.org/10.1113/JP282013
This record's URL: https://www.repository.cam.ac.uk/handle/1810/330558
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