Empathic pain evoked by sensory and emotional-communicative cues share common and process-specific neural representation
Abstract
Pain empathy can be evoked by multiple cues, particularly observation of acute pain inflictions or facial expressions of pain. Previous studies suggest that these cues commonly activate the insula and anterior cingulate, yet vicarious pain encompass pain-specific responses as well as unspecific processes (e.g., arousal) and overlapping activations are not sufficient to determine process-specific shared neural representations. We employed multivariate pattern analyses to fMRI data acquired during observation of noxious stimulation of body limbs (NS) and painful facial expressions (FE) and found spatially and functionally similar cross-modality (NS versus FE) whole-brain vicarious pain-predictive patterns. Further analyses consistently identified shared neural representations in the bilateral mid-insula. The vicarious pain patterns were not sensitive to respond to non-painful high-arousal negative stimuli but predicted self-experienced thermal pain. Finally, a domain-general vicarious pain pattern predictive of self-experienced pain but not arousal was developed. Our findings demonstrate shared pain-associated neural representations of vicarious pain.
Data availability
The functional MRI, numerical data as well as the Matlab scripts used to generate the figures have been deposited on the figshare repository under accession code 11994498 (https://figshare.com/articles/Vicarious_pain_dataset/11994498)Statistical and pattern weight maps are available on the Neurovault repository under collection 6332 (https://neurovault.org/collections/6332/). Statistical and pattern weight images are available on Neurovault
-
Vicarious pain datasetFigshare, Vicarious_pain_dataset/11994498.
Article and author information
Author details
Funding
National Natural Science Foundation of China (91632117)
- Benjamin Becker
National Natural Science Foundation of China (31700998)
- Keith M Kendrick
National Natural Science Foundation of China (31530032)
- Shuxia Yao
National Institute of Mental Health (R01 MH116026)
- Tor D Wager
National Institute of Biomedical Imaging and Bioengineering (R01EB026549)
- Tor D Wager
National Key Research and Development Program of China (2018YFA0701400)
- Benjamin Becker
Fundamental Research Funds for Central Universities (ZYGX2015Z002)
- Benjamin Becker
Science, Innovation and Technology Department of the Sichuan Province (2018JY0001)
- Benjamin Becker
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Alexander Shackman, University of Maryland, United States
Ethics
Human subjects: All participants provided written informed consent for study participation and consent to publish the data. The study and all procedures were approved by the local ethics committee at the University of Electronic Science and Technology of China (Approval ID: 298) and was in accordance with the most recent revision of the Declaration of Helsinki.
Version history
- Received: March 14, 2020
- Accepted: September 5, 2020
- Accepted Manuscript published: September 7, 2020 (version 1)
- Version of Record published: September 21, 2020 (version 2)
Copyright
© 2020, Zhou 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.
Metrics
-
- 5,458
- views
-
- 453
- downloads
-
- 71
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Neuroscience
Nociceptive sensory neurons convey pain-related signals to the CNS using action potentials. Loss-of-function mutations in the voltage-gated sodium channel NaV1.7 cause insensitivity to pain (presumably by reducing nociceptor excitability) but clinical trials seeking to treat pain by inhibiting NaV1.7 pharmacologically have struggled. This may reflect the variable contribution of NaV1.7 to nociceptor excitability. Contrary to claims that NaV1.7 is necessary for nociceptors to initiate action potentials, we show that nociceptors can achieve similar excitability using different combinations of NaV1.3, NaV1.7, and NaV1.8. Selectively blocking one of those NaV subtypes reduces nociceptor excitability only if the other subtypes are weakly expressed. For example, excitability relies on NaV1.8 in acutely dissociated nociceptors but responsibility shifts to NaV1.7 and NaV1.3 by the fourth day in culture. A similar shift in NaV dependence occurs in vivo after inflammation, impacting ability of the NaV1.7-selective inhibitor PF-05089771 to reduce pain in behavioral tests. Flexible use of different NaV subtypes exemplifies degeneracy – achieving similar function using different components – and compromises reliable modulation of nociceptor excitability by subtype-selective inhibitors. Identifying the dominant NaV subtype to predict drug efficacy is not trivial. Degeneracy at the cellular level must be considered when choosing drug targets at the molecular level.
-
- Neuroscience
Despite substantial progress in mapping the trajectory of network plasticity resulting from focal ischemic stroke, the extent and nature of changes in neuronal excitability and activity within the peri-infarct cortex of mice remains poorly defined. Most of the available data have been acquired from anesthetized animals, acute tissue slices, or infer changes in excitability from immunoassays on extracted tissue, and thus may not reflect cortical activity dynamics in the intact cortex of an awake animal. Here, in vivo two-photon calcium imaging in awake, behaving mice was used to longitudinally track cortical activity, network functional connectivity, and neural assembly architecture for 2 months following photothrombotic stroke targeting the forelimb somatosensory cortex. Sensorimotor recovery was tracked over the weeks following stroke, allowing us to relate network changes to behavior. Our data revealed spatially restricted but long-lasting alterations in somatosensory neural network function and connectivity. Specifically, we demonstrate significant and long-lasting disruptions in neural assembly architecture concurrent with a deficit in functional connectivity between individual neurons. Reductions in neuronal spiking in peri-infarct cortex were transient but predictive of impairment in skilled locomotion measured in the tapered beam task. Notably, altered neural networks were highly localized, with assembly architecture and neural connectivity relatively unaltered a short distance from the peri-infarct cortex, even in regions within ‘remapped’ forelimb functional representations identified using mesoscale imaging with anaesthetized preparations 8 weeks after stroke. Thus, using longitudinal two-photon microscopy in awake animals, these data show a complex spatiotemporal relationship between peri-infarct neuronal network function and behavioral recovery. Moreover, the data highlight an apparent disconnect between dramatic functional remapping identified using strong sensory stimulation in anaesthetized mice compared to more subtle and spatially restricted changes in individual neuron and local network function in awake mice during stroke recovery.