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      The Current View on the Paradox of Pain in Autism Spectrum Disorders

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          Abstract

          Autism spectrum disorder (ASD) is a neurodevelopmental disorder, which affects 1 in 44 children and may cause severe disabilities. Besides socio-communicational difficulties and repetitive behaviors, ASD also presents as atypical sensorimotor function and pain reactivity. While chronic pain is a frequent co-morbidity in autism, pain management in this population is often insufficient because of difficulties in pain evaluation, worsening their prognosis and perhaps driving higher mortality rates. Previous observations have tended to oversimplify the experience of pain in autism as being insensitive to painful stimuli. Various findings in the past 15 years have challenged and complicated this dogma. However, a relatively small number of studies investigates the physiological correlates of pain reactivity in ASD. We explore the possibility that atypical pain perception in people with ASD is mediated by alterations in pain perception, transmission, expression and modulation, and through interactions between these processes. These complex interactions may account for the great variability and sometimes contradictory findings from the studies. A growing body of evidence is challenging the idea of alterations in pain processing in ASD due to a single factor, and calls for an integrative view. We propose a model of the pain cycle that includes the interplay between the molecular and neurophysiological pathways of pain processing and it conscious appraisal that may interfere with pain reactivity and coping in autism. The role of social factors in pain-induced response is also discussed. Pain assessment in clinical care is mostly based on subjective rather than objective measures. This review clarifies the strong need for a consistent methodology, and describes innovative tools to cope with the heterogeneity of pain expression in ASD, enabling individualized assessment. Multiple measures, including self-reporting, informant reporting, clinician-assessed, and purely physiological metrics may provide more consistent results. An integrative view on the regulation of the pain cycle offers a more robust framework to characterize the experience of pain in autism.

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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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            The revised International Association for the Study of Pain definition of pain: concepts, challenges, and compromises

            The current International Association for the Study of Pain (IASP) definition of pain as "An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage" was recommended by the Subcommittee on Taxonomy and adopted by the IASP Council in 1979. This definition has become accepted widely by health care professionals and researchers in the pain field and adopted by several professional, governmental, and nongovernmental organizations, including the World Health Organization. In recent years, some in the field have reasoned that advances in our understanding of pain warrant a reevaluation of the definition and have proposed modifications. Therefore, in 2018, the IASP formed a 14-member, multinational Presidential Task Force comprising individuals with broad expertise in clinical and basic science related to pain, to evaluate the current definition and accompanying note and recommend whether they should be retained or changed. This review provides a synopsis of the critical concepts, the analysis of comments from the IASP membership and public, and the committee's final recommendations for revisions to the definition and notes, which were discussed over a 2-year period. The task force ultimately recommended that the definition of pain be revised to "An unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage," and that the accompanying notes be updated to a bulleted list that included the etymology. The revised definition and notes were unanimously accepted by the IASP Council early this year.
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              Neocortical excitation/inhibition balance in information processing and social dysfunction.

              Severe behavioural deficits in psychiatric diseases such as autism and schizophrenia have been hypothesized to arise from elevations in the cellular balance of excitation and inhibition (E/I balance) within neural microcircuitry. This hypothesis could unify diverse streams of pathophysiological and genetic evidence, but has not been susceptible to direct testing. Here we design and use several novel optogenetic tools to causally investigate the cellular E/I balance hypothesis in freely moving mammals, and explore the associated circuit physiology. Elevation, but not reduction, of cellular E/I balance within the mouse medial prefrontal cortex was found to elicit a profound impairment in cellular information processing, associated with specific behavioural impairments and increased high-frequency power in the 30-80 Hz range, which have both been observed in clinical conditions in humans. Consistent with the E/I balance hypothesis, compensatory elevation of inhibitory cell excitability partially rescued social deficits caused by E/I balance elevation. These results provide support for the elevated cellular E/I balance hypothesis of severe neuropsychiatric disease-related symptoms.
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                Author and article information

                Contributors
                Journal
                Front Psychiatry
                Front Psychiatry
                Front. Psychiatry
                Frontiers in Psychiatry
                Frontiers Media S.A.
                1664-0640
                22 July 2022
                2022
                : 13
                : 910824
                Affiliations
                [1] 1CNRS, Aquitaine Institute for Cognitive and Integrative Neuroscience, INCIA, UMR 5287, Université de Bordeaux , Bordeaux, France
                [2] 2Laboratoire EA 4136 – Handicap Activité Cognition Santé HACS, Collège Science de la Sante, Institut Universitaire des Sciences de la Réadaptation, Université de Bordeaux , Bordeaux, France
                [3] 3Centre Hospitalier Charles-Perrens, Pôle Universitaire de Psychiatrie de l’Enfant et de l’Adolescent , Bordeaux, France
                [4] 4Department of Neurology, University of Louisville , Louisville, KY, United States
                Author notes

                Edited by: Khaled Saad, Assiut University Hospital, Egypt

                Reviewed by: Catherine Caldwell-Harris, Boston University, United States; Islam Aud, Al-Azhar University, Egypt

                *Correspondence: Olena V. Bogdanova, olena.bogdanova@ 123456u-bordeaux.fr

                This article was submitted to Child and Adolescent Psychiatry, a section of the journal Frontiers in Psychiatry

                Article
                10.3389/fpsyt.2022.910824
                9352888
                35935443
                77ec36e0-4410-4c38-b2b1-9577872ead6c
                Copyright © 2022 Bogdanova, Bogdanov, Pizano, Bouvard, Cazalets, Mellen and Amestoy.

                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
                : 01 April 2022
                : 17 June 2022
                Page count
                Figures: 3, Tables: 1, Equations: 0, References: 289, Pages: 22, Words: 19621
                Categories
                Psychiatry
                Review

                Clinical Psychology & Psychiatry
                pain,autism,perception,reaction,evaluation,expression
                Clinical Psychology & Psychiatry
                pain, autism, perception, reaction, evaluation, expression

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