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      Words hurt: common and distinct neural substrates underlying nociceptive and semantic pain

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          Abstract

          Introduction

          Recent studies have shown that processing semantic pain, such as words associated with physical pain, modulates pain perception and enhances activity in regions of the pain matrix. A direct comparison between activations due to noxious stimulation and processing of words conveying physical pain may clarify whether and to what extent the neural substrates of nociceptive pain are shared by semantic pain. Pain is triggered also by experiences of social exclusion, rejection or loss of significant others (the so-called social pain), therefore words expressing social pain may modulate pain perception similarly to what happens with words associated with physical pain. This event-related fMRI study aims to compare the brain activity related to perceiving nociceptive pain and that emerging from processing semantic pain, i.e., words related to either physical or social pain, in order to identify common and distinct neural substrates.

          Methods

          Thirty-four healthy women underwent two fMRI sessions each. In the Semantic session, participants were presented with positive words, negative pain-unrelated words, physical pain-related words, and social pain-related words. In the Nociceptive session, participants received cutaneous mechanical stimulations that could be either painful or not. During both sessions, participants were asked to rate the unpleasantness of each stimulus. Linguistic stimuli were also rated in terms of valence, arousal, pain relatedness, and pain intensity, immediately after the Semantic session.

          Results

          In the Nociceptive session, the ‘nociceptive stimuli’ vs. ‘non-nociceptive stimuli’ contrast revealed extensive activations in SI, SII, insula, cingulate cortex, thalamus, and dorsolateral prefrontal cortex. In the Semantic session, words associated with social pain, compared to negative pain-unrelated words, showed increased activity in most of the same areas, whereas words associated with physical pain, compared to negative pain-unrelated words, only activated the left supramarginal gyrus and partly the postcentral gyrus.

          Discussion

          Our results confirm that semantic pain partly shares the neural substrates of nociceptive pain. Specifically, social pain-related words activate a wide network of regions, mostly overlapping with those pertaining to the affective-motivational aspects of nociception, whereas physical pain-related words overlap with a small cluster including regions related to the sensory-discriminative aspects of nociception. However, most regions of overlap are differentially activated in different conditions.

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          Most cited references127

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          The assessment and analysis of handedness: The Edinburgh inventory

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            Emotional processing in anterior cingulate and medial prefrontal cortex.

            Negative emotional stimuli activate a broad network of brain regions, including the medial prefrontal (mPFC) and anterior cingulate (ACC) cortices. An early influential view dichotomized these regions into dorsal-caudal cognitive and ventral-rostral affective subdivisions. In this review, we examine a wealth of recent research on negative emotions in animals and humans, using the example of fear or anxiety, and conclude that, contrary to the traditional dichotomy, both subdivisions make key contributions to emotional processing. Specifically, dorsal-caudal regions of the ACC and mPFC are involved in appraisal and expression of negative emotion, whereas ventral-rostral portions of the ACC and mPFC have a regulatory role with respect to limbic regions involved in generating emotional responses. Moreover, this new framework is broadly consistent with emerging data on other negative and positive emotions. Published by Elsevier Ltd.
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              Empathy for pain involves the affective but not sensory components of pain.

              Our ability to have an experience of another's pain is characteristic of empathy. Using functional imaging, we assessed brain activity while volunteers experienced a painful stimulus and compared it to that elicited when they observed a signal indicating that their loved one--present in the same room--was receiving a similar pain stimulus. Bilateral anterior insula (AI), rostral anterior cingulate cortex (ACC), brainstem, and cerebellum were activated when subjects received pain and also by a signal that a loved one experienced pain. AI and ACC activation correlated with individual empathy scores. Activity in the posterior insula/secondary somatosensory cortex, the sensorimotor cortex (SI/MI), and the caudal ACC was specific to receiving pain. Thus, a neural response in AI and rostral ACC, activated in common for "self" and "other" conditions, suggests that the neural substrate for empathic experience does not involve the entire "pain matrix." We conclude that only that part of the pain network associated with its affective qualities, but not its sensory qualities, mediates empathy.
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                Author and article information

                Contributors
                Journal
                Front Neurosci
                Front Neurosci
                Front. Neurosci.
                Frontiers in Neuroscience
                Frontiers Media S.A.
                1662-4548
                1662-453X
                27 September 2023
                2023
                : 17
                : 1234286
                Affiliations
                [1] 1Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia , Modena, Italy
                [2] 2Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia , Modena, Italy
                [3] 3Oncology and Palliative Care Units, Civil Hospital Carpi, USL , Carpi, Italy
                [4] 4Hematology Unit and Chair, Azienda Ospedaliera Universitaria di Modena , Modena, Italy
                Author notes

                Edited by: Mariella Pazzaglia, Sapienza University of Rome, Italy

                Reviewed by: Irene Peláez, Rey Juan Carlos University, Spain; Diego Galán, Rey Juan Carlos University, Spain; Keith Michael Vogt, University of Pittsburgh, United States

                *Correspondence: Francesca Benuzzi, francesca.benuzzi@ 123456unimore.it

                These authors share last authorship

                Article
                10.3389/fnins.2023.1234286
                10565001
                37829724
                fea6d514-43b6-4174-9eae-7b0adeb5a2ad
                Copyright © 2023 Borelli, Benuzzi, Ballotta, Bandieri, Luppi, Cacciari, Porro and Lui.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 04 June 2023
                : 01 September 2023
                Page count
                Figures: 8, Tables: 5, Equations: 0, References: 127, Pages: 19, Words: 14685
                Categories
                Neuroscience
                Original Research
                Custom metadata
                Perception Science

                Neurosciences
                pain,semantics,language,words,social pain-related words,physical pain-related words,nociception,fmri

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