Increased functional connectivity between limbic brain areas in healthy individuals with high versus low sensitivity to cold pain: A resting state fMRI study

Hadas Grouper, Martin Löffler, Herta Flor, Elon Eisenberg, Dorit Pud

Research output: Contribution to journalArticlepeer-review


Background The representation of variability in sensitivity to pain by differences in neural connectivity patterns and its association with psychological factors needs further investigation. This study assessed differences in resting-state functional connectivity (rsFC) and its association to cognitive-affective aspects of pain in two groups of healthy subjects with low versus high sensitivity to pain (LSP vs. HSP). We hypothesized that HSP will show stronger connectivity in brain regions involved in the affective-motivational processing of pain and that this higher connectivity would be related to negative affective and cognitive evaluations of pain. Methods Forty-eight healthy subjects were allocated to two groups according to their tolerability to cold stimulation (cold pressor test, CPT, 1◦C). Group LSP (N = 24) reached the cut-off time of 180±0 sec and group HSP tolerated the CPT for an average of 13±4.8 sec. Heat, cold and mechanical evoked pain were measured, as well as pain-catastrophizing (PCS), depression, anxiety and stress (DASS-21). All subjects underwent resting state fMRI. ROI-to-ROI analysis was performed. Results In comparison to the LSP, the HSP had stronger interhemispheric connectivity of the amygdala (p = 0.01) and between the amygdala and nucleus accumbens (NAc) (p = 0.01). Amygdala connectivity was associated with higher pain catastrophizing in the HSP only (p<0.01). Conclusions These findings suggest that high sensitivity to pain may be reflected by neural circuits involved in affective and motivational aspects of pain. To what extent this connectivity within limbic brain structures relates to higher alertness and more profound withdrawal behavior to aversive events needs to be further investigated.

Original languageEnglish
Article numbere0267170
JournalPLoS ONE
Issue number4
StatePublished - Apr 2022

Bibliographical note

Publisher Copyright:
Copyright: © 2022 Grouper et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


  • Amygdala/physiology
  • Brain/diagnostic imaging
  • Brain Mapping
  • Humans
  • Magnetic Resonance Imaging
  • Neural Pathways/physiology
  • Pain/diagnostic imaging

ASJC Scopus subject areas

  • General


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