Regional and whole-brain neurofunctional alterations during pain empathic processing of physical but not affective pain in migraine patients

Abstract Background Accumulating evidence suggests that migraine patients present abnormal brain responses to salient sensory and emotional stimuli. However, it is still unclear whether this is a generalized or domain-specific phenomenon. Employing a well-validated fMRI paradigm, we investigated pai...

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Main Authors: Dan Liu, Menghan Li, Heng Jiang, Yiqi Mi, Xiaolei Xu, Yali Zhou, Yaxian Hou, Yuquan Shen, Michael Maes, Xiao Xiao, Feng Zhou, Luca Giani, Keith M. Kendrick, Benjamin Becker, Stefania Ferraro
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Language:English
Published: BMC 2025-06-01
Series:The Journal of Headache and Pain
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Online Access:https://doi.org/10.1186/s10194-025-02051-x
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author Dan Liu
Menghan Li
Heng Jiang
Yiqi Mi
Xiaolei Xu
Yali Zhou
Yaxian Hou
Yuquan Shen
Michael Maes
Xiao Xiao
Feng Zhou
Luca Giani
Keith M. Kendrick
Benjamin Becker
Stefania Ferraro
author_facet Dan Liu
Menghan Li
Heng Jiang
Yiqi Mi
Xiaolei Xu
Yali Zhou
Yaxian Hou
Yuquan Shen
Michael Maes
Xiao Xiao
Feng Zhou
Luca Giani
Keith M. Kendrick
Benjamin Becker
Stefania Ferraro
author_sort Dan Liu
collection DOAJ
description Abstract Background Accumulating evidence suggests that migraine patients present abnormal brain responses to salient sensory and emotional stimuli. However, it is still unclear whether this is a generalized or domain-specific phenomenon. Employing a well-validated fMRI paradigm, we investigated pain empathic reactivity across two domains: observation of physical pain (noxious stimulation) and affective pain (facial expressions). On the basis of a generalized hyperexcitability/hyperreactivity in migraine, we hypothesized abnormal responses to both dimensions of pain empathy. Methods We collected fMRI and psychometric data from 21 migraine patients and matched controls. Univariate and multivariate neuroimaging analyses were utilized to examine domain-specific dysregulations in (a) neural reactivity in meta-analytically defined shared regions of pain-empathy processing, and (b) whole-brain neurofunctional signatures of physical and affective pain empathy (VPS, Zhou et al., 2020). Logistic regression models and machine learning-based classification were employed to determine differences between groups (migraine or control). Results Migraine patients exhibit increased neural responses during empathy for physical pain in the bilateral inferior frontal gyrus (slightly more pronounced on the right side), with alterations on the right significantly associated with the pain experienced during the attack. On the whole-brain level, the predictive accuracy of the VPS for physical pain empathy was shown to be significantly higher for patients as compared to controls, reaching 100% accuracy. Across analyses, we did not find evidence of altered empathy processing for affective pain. Conclusions Contrary to our hypothesis, our results indicate that migraine patients present a domain-specific increased brain responsivity, localized in the bilateral inferior frontal gyrus but also extending to subtle whole brain patterns, during empathy for physical pain stimuli, but not during empathy for affective pain. Based on the evidence that the neural pathways for empathy for physical pain and experimental pain robustly overlap, these results indicate a specific hyperresponsivity of the pain pathways, with the inferior frontal gyrus likely playing a regulatory role in modulating pain-related processes. Finally, the results underscore the translational application potential of neuroaffective multivariate signatures as neuromarkers for pathological dysregulations in affective and pain-related processes.
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spelling doaj-art-246cecfaff044039bb2b2de5442ec8b32025-08-20T03:45:32ZengBMCThe Journal of Headache and Pain1129-23772025-06-0126111810.1186/s10194-025-02051-xRegional and whole-brain neurofunctional alterations during pain empathic processing of physical but not affective pain in migraine patientsDan Liu0Menghan Li1Heng Jiang2Yiqi Mi3Xiaolei Xu4Yali Zhou5Yaxian Hou6Yuquan Shen7Michael Maes8Xiao Xiao9Feng Zhou10Luca Giani11Keith M. Kendrick12Benjamin Becker13Stefania Ferraro14The Center of Psychosomatic Medicine, Sichuan Provincial Center for Mental Health, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of ChinaThe Center of Psychosomatic Medicine, Sichuan Provincial Center for Mental Health, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of ChinaThe Center of Psychosomatic Medicine, Sichuan Provincial Center for Mental Health, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of ChinaThe Center of Psychosomatic Medicine, Sichuan Provincial Center for Mental Health, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of ChinaSchool of Psychology, Shandong Normal UniversityThe Center of Psychosomatic Medicine, Sichuan Provincial Center for Mental Health, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of ChinaThe Center of Psychosomatic Medicine, Sichuan Provincial Center for Mental Health, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of ChinaDepartment of Rehabilitation Medicine, The First People’s Hospital of Longquanyi DistrictKey Laboratory of Psychosomatic Medicine, Chinese Academy of Medical SciencesBehavioral and Cognitive Neuroscience Center, Institute of Science and Technology for Brain-Inspired Intelligence, Fudan UniversityFaculty of Psychology, Southwest University, Chongqing, China, Key Laboratory of Cognition and Personality, Ministry of EducationIstituti Clinici Scientifici Maugeri IRCCS, Neurological Rehabilitation Unit of Milano InstituteMinistry of Education Key Laboratory for Neuroinformation, School of Life Science and Technology, University of Electronic Science and Technology of ChinaThe State Key Laboratory of Brain and Cognitive Sciences, The University of Hong KongThe Center of Psychosomatic Medicine, Sichuan Provincial Center for Mental Health, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of ChinaAbstract Background Accumulating evidence suggests that migraine patients present abnormal brain responses to salient sensory and emotional stimuli. However, it is still unclear whether this is a generalized or domain-specific phenomenon. Employing a well-validated fMRI paradigm, we investigated pain empathic reactivity across two domains: observation of physical pain (noxious stimulation) and affective pain (facial expressions). On the basis of a generalized hyperexcitability/hyperreactivity in migraine, we hypothesized abnormal responses to both dimensions of pain empathy. Methods We collected fMRI and psychometric data from 21 migraine patients and matched controls. Univariate and multivariate neuroimaging analyses were utilized to examine domain-specific dysregulations in (a) neural reactivity in meta-analytically defined shared regions of pain-empathy processing, and (b) whole-brain neurofunctional signatures of physical and affective pain empathy (VPS, Zhou et al., 2020). Logistic regression models and machine learning-based classification were employed to determine differences between groups (migraine or control). Results Migraine patients exhibit increased neural responses during empathy for physical pain in the bilateral inferior frontal gyrus (slightly more pronounced on the right side), with alterations on the right significantly associated with the pain experienced during the attack. On the whole-brain level, the predictive accuracy of the VPS for physical pain empathy was shown to be significantly higher for patients as compared to controls, reaching 100% accuracy. Across analyses, we did not find evidence of altered empathy processing for affective pain. Conclusions Contrary to our hypothesis, our results indicate that migraine patients present a domain-specific increased brain responsivity, localized in the bilateral inferior frontal gyrus but also extending to subtle whole brain patterns, during empathy for physical pain stimuli, but not during empathy for affective pain. Based on the evidence that the neural pathways for empathy for physical pain and experimental pain robustly overlap, these results indicate a specific hyperresponsivity of the pain pathways, with the inferior frontal gyrus likely playing a regulatory role in modulating pain-related processes. Finally, the results underscore the translational application potential of neuroaffective multivariate signatures as neuromarkers for pathological dysregulations in affective and pain-related processes.https://doi.org/10.1186/s10194-025-02051-xMigrainefMRIEmpathy for painPain processingInferior frontal gyrus
spellingShingle Dan Liu
Menghan Li
Heng Jiang
Yiqi Mi
Xiaolei Xu
Yali Zhou
Yaxian Hou
Yuquan Shen
Michael Maes
Xiao Xiao
Feng Zhou
Luca Giani
Keith M. Kendrick
Benjamin Becker
Stefania Ferraro
Regional and whole-brain neurofunctional alterations during pain empathic processing of physical but not affective pain in migraine patients
The Journal of Headache and Pain
Migraine
fMRI
Empathy for pain
Pain processing
Inferior frontal gyrus
title Regional and whole-brain neurofunctional alterations during pain empathic processing of physical but not affective pain in migraine patients
title_full Regional and whole-brain neurofunctional alterations during pain empathic processing of physical but not affective pain in migraine patients
title_fullStr Regional and whole-brain neurofunctional alterations during pain empathic processing of physical but not affective pain in migraine patients
title_full_unstemmed Regional and whole-brain neurofunctional alterations during pain empathic processing of physical but not affective pain in migraine patients
title_short Regional and whole-brain neurofunctional alterations during pain empathic processing of physical but not affective pain in migraine patients
title_sort regional and whole brain neurofunctional alterations during pain empathic processing of physical but not affective pain in migraine patients
topic Migraine
fMRI
Empathy for pain
Pain processing
Inferior frontal gyrus
url https://doi.org/10.1186/s10194-025-02051-x
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