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      Journal of Pain Research (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on reporting of high-quality laboratory and clinical findings in all fields of pain research and the prevention and management of pain. Sign up for email alerts here.

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      Construction And Analysis Of The Time-Evolving Pain-Related Brain Network Using Literature Mining

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          Abstract

          Purpose

          We aimed to quantitatively investigate how the neuroscience field developed over time in terms of its concept on how pain is represented in the brain and compare the research trends of pain with those of mental disorders through literature mining of accumulated published articles.

          Methods

          The abstracts and publication years of 137,525 pain-related articles were retrieved from the PubMed database. We defined 22 pain-related brain regions that appeared more than 100 times in the retrieved abstracts. Time-evolving networks of pain-related brain regions were constructed using the co-occurrence frequency. The state-space model was implemented to capture the trend patterns of the pain-related brain regions and the patterns were compared with those of mental disorders.

          Results

          The number of pain-related abstracts including brain areas steadily increased; however, the relative frequency of each brain region showed different patterns. According to the chronological patterns of relative frequencies, pain-related brain regions were clustered into three groups: rising, falling, and consistent. The network of pain-related brain regions extended over time from localized regions (mainly including brain stem and diencephalon) to wider cortical/subcortical regions. In the state-space model, the relative frequency trajectory of pain-related brain regions gradually became closer to that of mental disorder-related brain regions.

          Conclusion

          Temporal changes of pain-related brain regions in the abstracts indicate that emotional/cognitive aspects of pain have been gradually emphasized. The networks of pain-related brain regions imply perspective changes on pain from the simple percept to the multidimensional experience. Based on the notable occurrence patterns of the cerebellum and motor cortex, we suggest that motor-related areas will be actively explored in pain studies.

          Most cited references36

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          Cognitive and emotional influences in anterior cingulate cortex.

          Bush, Luu, Posner (2000)
          Anterior cingulate cortex (ACC) is a part of the brain's limbic system. Classically, this region has been related to affect, on the basis of lesion studies in humans and in animals. In the late 1980s, neuroimaging research indicated that ACC was active in many studies of cognition. The findings from EEG studies of a focal area of negativity in scalp electrodes following an error response led to the idea that ACC might be the brain's error detection and correction device. In this article, these various findings are reviewed in relation to the idea that ACC is a part of a circuit involved in a form of attention that serves to regulate both cognitive and emotional processing. Neuroimaging studies showing that separate areas of ACC are involved in cognition and emotion are discussed and related to results showing that the error negativity is influenced by affect and motivation. In addition, the development of the emotional and cognitive roles of ACC are discussed, and how the success of this regulation in controlling responses might be correlated with cingulate size. Finally, some theories are considered about how the different subdivisions of ACC might interact with other cortical structures as a part of the circuits involved in the regulation of mental and emotional activity.
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            Functional imaging of brain responses to pain. A review and meta-analysis (2000).

            Brain responses to pain, assessed through positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) are reviewed. Functional activation of brain regions are thought to be reflected by increases in the regional cerebral blood flow (rCBF) in PET studies, and in the blood oxygen level dependent (BOLD) signal in fMRI. rCBF increases to noxious stimuli are almost constantly observed in second somatic (SII) and insular regions, and in the anterior cingulate cortex (ACC), and with slightly less consistency in the contralateral thalamus and the primary somatic area (SI). Activation of the lateral thalamus, SI, SII and insula are thought to be related to the sensory-discriminative aspects of pain processing. SI is activated in roughly half of the studies, and the probability of obtaining SI activation appears related to the total amount of body surface stimulated (spatial summation) and probably also by temporal summation and attention to the stimulus. In a number of studies, the thalamic response was bilateral, probably reflecting generalised arousal in reaction to pain. ACC does not seem to be involved in coding stimulus intensity or location but appears to participate in both the affective and attentional concomitants of pain sensation, as well as in response selection. ACC subdivisions activated by painful stimuli partially overlap those activated in orienting and target detection tasks, but are distinct from those activated in tests involving sustained attention (Stroop, etc.). In addition to ACC, increased blood flow in the posterior parietal and prefrontal cortices is thought to reflect attentional and memory networks activated by noxious stimulation. Less noted but frequent activation concerns motor-related areas such as the striatum, cerebellum and supplementary motor area, as well as regions involved in pain control such as the periaqueductal grey. In patients, chronic spontaneous pain is associated with decreased resting rCBF in contralateral thalamus, which may be reverted by analgesic procedures. Abnormal pain evoked by innocuous stimuli (allodynia) has been associated with amplification of the thalamic, insular and SII responses, concomitant to a paradoxical CBF decrease in ACC. It is argued that imaging studies of allodynia should be encouraged in order to understand central reorganisations leading to abnormal cortical pain processing. A number of brain areas activated by acute pain, particularly the thalamus and anterior cingulate, also show increases in rCBF during analgesic procedures. Taken together, these data suggest that hemodynamic responses to pain reflect simultaneously the sensory, cognitive and affective dimensions of pain, and that the same structure may both respond to pain and participate in pain control. The precise biochemical nature of these mechanisms remains to be investigated.
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              Central mechanisms of pathological pain.

              Chronic pain is a major challenge to clinical practice and basic science. The peripheral and central neural networks that mediate nociception show extensive plasticity in pathological disease states. Disease-induced plasticity can occur at both structural and functional levels and is manifest as changes in individual molecules, synapses, cellular function and network activity. Recent work has yielded a better understanding of communication within the neural matrix of physiological pain and has also brought important advances in concepts of injury-induced hyperalgesia and tactile allodynia and how these might contribute to the complex, multidimensional state of chronic pain. This review focuses on the molecular determinants of network plasticity in the central nervous system (CNS) and discusses their relevance to the development of new therapeutic approaches.
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                Author and article information

                Journal
                J Pain Res
                J Pain Res
                JPR
                jpainres
                Journal of Pain Research
                Dove
                1178-7090
                16 October 2019
                2019
                : 12
                : 2891-2903
                Affiliations
                [1 ]Department of Physiology, College of Korean Medicine, Gachon University , Seongnam 13120, Republic of Korea
                Author notes
                Correspondence: Chang-Eop Kim Department of Physiology, College of Korean Medicine, Gachon University , 1342, Seongnam-daero, Sujeong-gu, Seongnam-si, Gyeonggi-do, Repubic of KoreaTel/fax +82-31-750-5416 Email eopchang@gachon.ac.kr
                Author information
                http://orcid.org/0000-0002-3847-1938
                http://orcid.org/0000-0001-8281-9148
                Article
                217036
                10.2147/JPR.S217036
                6801488
                31802931
                205ffa17-4e61-4650-91c5-667639c81bf0
                © 2019 Oh et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 24 May 2019
                : 17 September 2019
                Page count
                Figures: 9, Tables: 2, References: 49, Pages: 13
                Categories
                Original Research

                Anesthesiology & Pain management
                pain,pain-related brain regions,pain-related brain networks,pain research trend analysis,literature mining,text mining,mental disorders and pain

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