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      Gray matter alterations in chronic pain: A network-oriented meta-analytic approach

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          Abstract

          Several studies have attempted to characterize morphological brain changes due to chronic pain. Although it has repeatedly been suggested that longstanding pain induces gray matter modifications, there is still some controversy surrounding the direction of the change (increase or decrease in gray matter) and the role of psychological and psychiatric comorbidities. In this study, we propose a novel, network-oriented, meta-analytic approach to characterize morphological changes in chronic pain. We used network decomposition to investigate whether different kinds of chronic pain are associated with a common or specific set of altered networks. Representational similarity techniques, network decomposition and model-based clustering were employed: i) to verify the presence of a core set of brain areas commonly modified by chronic pain; ii) to investigate the involvement of these areas in a large-scale network perspective; iii) to study the relationship between altered networks and; iv) to find out whether chronic pain targets clusters of areas. Our results showed that chronic pain causes both core and pathology-specific gray matter alterations in large-scale networks. Common alterations were observed in the prefrontal regions, in the anterior insula, cingulate cortex, basal ganglia, thalamus, periaqueductal gray, post- and pre-central gyri and inferior parietal lobule. We observed that the salience and attentional networks were targeted in a very similar way by different chronic pain pathologies. Conversely, alterations in the sensorimotor and attention circuits were differentially targeted by chronic pain pathologies. Moreover, model-based clustering revealed that chronic pain, in line with some neurodegenerative diseases, selectively targets some large-scale brain networks. Altogether these findings indicate that chronic pain can be better conceived and studied in a network perspective.

          Highlights

          • Chronic pain causes both core and pathology-specific.

          • GM alterations in brain networks.

          • Model-based clustering revealed that chronic pain selectively targets brain networks.

          • Chronic pain can be better conceived and studied in a network perspective.

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          Most cited references83

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          Shape shifting pain: chronification of back pain shifts brain representation from nociceptive to emotional circuits.

          Chronic pain conditions are associated with abnormalities in brain structure and function. Moreover, some studies indicate that brain activity related to the subjective perception of chronic pain may be distinct from activity for acute pain. However, the latter are based on observations from cross-sectional studies. How brain activity reorganizes with transition from acute to chronic pain has remained unexplored. Here we study this transition by examining brain activity for rating fluctuations of back pain magnitude. First we compared back pain-related brain activity between subjects who have had the condition for ∼2 months with no prior history of back pain for 1 year (early, acute/subacute back pain group, n = 94), to subjects who have lived with back pain for >10 years (chronic back pain group, n = 59). In a subset of subacute back pain patients, we followed brain activity for back pain longitudinally over a 1-year period, and compared brain activity between those who recover (recovered acute/sub-acute back pain group, n = 19) and those in which the back pain persists (persistent acute/sub-acute back pain group, n = 20; based on a 20% decrease in intensity of back pain in 1 year). We report results in relation to meta-analytic probabilistic maps related to the terms pain, emotion, and reward (each map is based on >200 brain imaging studies, derived from neurosynth.org). We observed that brain activity for back pain in the early, acute/subacute back pain group is limited to regions involved in acute pain, whereas in the chronic back pain group, activity is confined to emotion-related circuitry. Reward circuitry was equally represented in both groups. In the recovered acute/subacute back pain group, brain activity diminished in time, whereas in the persistent acute/subacute back pain group, activity diminished in acute pain regions, increased in emotion-related circuitry, and remained unchanged in reward circuitry. The results demonstrate that brain representation for a constant percept, back pain, can undergo large-scale shifts in brain activity with the transition to chronic pain. These observations challenge long-standing theoretical concepts regarding brain and mind relationships, as well as provide important novel insights regarding definitions and mechanisms of chronic pain.
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            Towards a theory of chronic pain.

            In this review, we integrate recent human and animal studies from the viewpoint of chronic pain. First, we briefly review the impact of chronic pain on society and address current pitfalls of its definition and clinical management. Second, we examine pain mechanisms via nociceptive information transmission cephalad and its impact and interaction with the cortex. Third, we present recent discoveries on the active role of the cortex in chronic pain, with findings indicating that the human cortex continuously reorganizes as it lives in chronic pain. We also introduce data emphasizing that distinct chronic pain conditions impact on the cortex in unique patterns. Fourth, animal studies regarding nociceptive transmission, recent evidence for supraspinal reorganization during pain, the necessity of descending modulation for maintenance of neuropathic behavior, and the impact of cortical manipulations on neuropathic pain is also reviewed. We further expound on the notion that chronic pain can be reformulated within the context of learning and memory, and demonstrate the relevance of the idea in the design of novel pharmacotherapies. Lastly, we integrate the human and animal data into a unified working model outlining the mechanism by which acute pain transitions into a chronic state. It incorporates knowledge of underlying brain structures and their reorganization, and also includes specific variations as a function of pain persistence and injury type, thereby providing mechanistic descriptions of several unique chronic pain conditions within a single model.
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              Effective treatment of chronic low back pain in humans reverses abnormal brain anatomy and function.

              Chronic pain is associated with reduced brain gray matter and impaired cognitive ability. In this longitudinal study, we assessed whether neuroanatomical and functional abnormalities were reversible and dependent on treatment outcomes. We acquired MRI scans from chronic low back pain (CLBP) patients before (n = 18) and 6 months after (spine surgery or facet joint injections; n = 14) treatment. In addition, we scanned 16 healthy controls, 10 of which returned 6 months after the first visit. We performed cortical thickness analysis on structural MRI scans, and subjects performed a cognitive task during the functional MRI. We compared patients and controls, as well as patients before versus after treatment. After treatment, patients had increased cortical thickness in the left dorsolateral prefrontal cortex (DLPFC), which was thinner before treatment compared with controls. Increased DLPFC thickness correlated with the reduction of both pain and physical disability. Additionally, increased thickness in primary motor cortex was associated specifically with reduced physical disability, and right anterior insula was associated specifically with reduced pain. Left DLPFC activity during an attention-demanding cognitive task was abnormal before treatment, but normalized following treatment. These data indicate that functional and structural brain abnormalities-specifically in the left DLPFC-are reversible, suggesting that treating chronic pain can restore normal brain function in humans.
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                Author and article information

                Contributors
                Journal
                Neuroimage Clin
                Neuroimage Clin
                NeuroImage : Clinical
                Elsevier
                2213-1582
                16 April 2014
                16 April 2014
                2014
                : 4
                : 676-686
                Affiliations
                [a ]GCS fMRI, Koelliker Hospital, Department of Psychology, University of Turin, Turin, Italy
                [b ]Functional Neuroimaging and Complex Systems Group, Department of Psychology, University of Turin, Turin, Italy
                [c ]Department of Psychology, University of Turin, Turin, Italy
                [d ]Department of Neuroscience, AOU San Giovanni Battista, Turin, Italy
                [e ]Psycho-Oncology and Clinical Psychology Unit, University of Turin, Città della Salute e della Scienza, Turin, Italy
                Author notes
                [* ]Corresponding author at: Department of Psychology, Via Po 14, Turin 10123, Italy. franco.cauda@ 123456unito.it
                Article
                S2213-1582(14)00051-5
                10.1016/j.nicl.2014.04.007
                4053643
                24936419
                5ea8f09f-433e-43ac-bad5-bcb2b11bdc50
                © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

                History
                : 23 January 2014
                : 25 March 2014
                : 12 April 2014
                Categories
                Article

                chronic pain,brain networks,gray matter alterations,voxel-based metaanalysis

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