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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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      Sex-specific impact of early-life adversity on chronic pain: a large population-based study in Japan

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          Abstract

          Background

          Responses to early-life adversity may differ by sex. We investigated the sex-specific impact of early-life adversity on chronic pain, chronic multisite pain, and somatizing tendency with chronic pain.

          Methods

          We examined 4229 respondents aged 20–79 years who participated in the Pain Associated Cross-Sectional Epidemiological Survey in Japan. Outcomes were: 1) chronic pain prevalence, 2) multisite pain (≥3 sites) prevalence, and 3) multiple somatic symptoms (≥3 symptoms) among respondents with chronic pain related to the presence or absence of early-life adversity.

          Multivariable-adjusted odds ratios (ORs) were calculated with 95% confidence intervals using a logistic regression model including age, smoking status, exercise routine, sleep time, body mass index, household expenditure, and the full distribution of scores on the Mental Health Inventory-5. We further adjusted for pain intensity when we analyzed the data for respondents with chronic pain.

          Results

          The prevalence of chronic pain was higher among respondents reporting the presence of early-life adversity compared with those reporting its absence, with multivariable ORs of 1.62 (1.22–2.15, p<0.01) in men and 1.47 (1.13–1.90, p<0.01) in women. Among women with chronic pain, early-life adversity was associated with multisite pain and multiple somatic symptoms; multivariable ORs were 1.78 (1.22–2.60, p<0.01) for multisite pain and 1.89 (1.27–2.83, p<0.01) for ≥3 somatic symptoms. No associations were observed between early-life adversity and chronic multisite pain or multiple somatic symptoms among men with chronic pain.

          Conclusion

          Early-life adversity may be linked to a higher prevalence of chronic pain among both sexes and to multisite pain and somatizing tendency among women with chronic pain.

          Most cited references22

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          Abnormalities in hippocampal functioning with persistent pain.

          Chronic pain patients exhibit increased anxiety, depression, and deficits in learning and memory. Yet how persistent pain affects the key brain area regulating these behaviors, the hippocampus, has remained minimally explored. In this study we investigated the impact of spared nerve injury (SNI) neuropathic pain in mice on hippocampal-dependent behavior and underlying cellular and molecular changes. In parallel, we measured the hippocampal volume of three groups of chronic pain patients. We found that SNI animals were unable to extinguish contextual fear and showed increased anxiety-like behavior. Additionally, SNI mice compared with Sham animals exhibited hippocampal (1) reduced extracellular signal-regulated kinase expression and phosphorylation, (2) decreased neurogenesis, and (3) altered short-term synaptic plasticity. To relate the observed hippocampal abnormalities with human chronic pain, we measured the volume of human hippocampus in chronic back pain (CBP), complex regional pain syndrome (CRPS), and osteoarthritis patients (OA). Compared with controls, CBP and CRPS, but not OA, had significantly less bilateral hippocampal volume. These results indicate that hippocampus-mediated behavior, synaptic plasticity, and neurogenesis are abnormal in neuropathic rodents. The changes may be related to the reduction in hippocampal volume we see in chronic pain patients, and these abnormalities may underlie learning and emotional deficits commonly observed in such patients.
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            Sex differences in pain and analgesia: the role of gonadal hormones.

            There is now strong evidence for sex differences in pain and analgesia. These differences imply that gonadal steroid hormones such as estradiol and testosterone modulate sensitivity to pain and analgesia. The goal of this review is to present an overview of gonadal steroid modulation of pain and analgesia in animals and humans, and to describe mechanisms by which males' and females' biology may differentially predispose them to pain and to analgesic effects of drugs and stress. Evidence is presented to demonstrate that sex differences in pain and analgesia may be both quantitative and qualitative in nature. Current research suggests that sex-specific management of clinical pain will be a reality in the not-so-distant future.
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              Hippocampal changes associated with early-life adversity and vulnerability to depression.

              Smaller hippocampal volume has been reported in some adult and pediatric studies of unipolar major depressive disorder. It is not clear whether the smaller hippocampal volume precedes or is a consequence of the illness. Early-life adversity is associated with both smaller hippocampal volume and increased vulnerability to depressive disorder. Hippocampal changes may mediate the relationship between early-life adversity and depressive illness in a subset of patients. However, there are no reports of longitudinal clinical studies that have examined this issue. Thirty adolescents with unipolar major depressive disorder, 22 adolescent volunteers with no personal history of a psychiatric illness including depression but who were at high risk for developing depression by virtue of parental depression (high-risk group), and 35 adolescent volunteers with no personal or family history of a psychiatric disorder (control subjects) underwent volumetric magnetic resonance imaging studies. Information was also gathered on early and recent adverse experiences with standard interviews. The participants were followed for up to 5 years to assess the onset and clinical course of depression. Depressed and high-risk groups had significantly smaller left and right hippocampal volumes than control subjects. Higher levels of early-life adversity were associated with smaller hippocampal volumes. Smaller hippocampal volume partially mediated the effect of early-life adversity on depression during longitudinal follow-up. Smaller hippocampal volume in adolescents at high risk for depression suggests that it may be a vulnerability marker for the illness. Early-life adversity may interact with genetic vulnerability to induce hippocampal changes, potentially increasing the risk for depressive disorder. 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                J Pain Res
                J Pain Res
                Journal of Pain Research
                Journal of Pain Research
                Dove Medical Press
                1178-7090
                2017
                16 February 2017
                : 10
                : 427-433
                Affiliations
                [1 ]Public Health, Department of Social Medicine, Osaka University Graduate School of Medicine, Suita, Osaka
                [2 ]Center for Pain Management, Osaka University Hospital, Suita, Osaka
                [3 ]Department of Medical Research and Management for Musculoskeletal Pain, 22nd Century Medical and Research Center, Faculty of Medicine, The University of Tokyo, Tokyo
                [4 ]Japan Labour Health & Welfare Organization, Tokyo
                [5 ]Hyogo Institute for Traumatic Stress, Kobe
                [6 ]Department of Prosthetics & Orthotics and Assistive Technology, Faculty of Medical Technology, Niigata University of Health and Welfare, Niigata, Japan
                Author notes
                Correspondence: Hiroyasu Iso, Public Health, Department of Social Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan, Tel +81 6 6879 3911, Fax +81 6 6879 3919, Email iso@ 123456pbhel.med.osaka-u.ac.jp
                Article
                jpr-10-427
                10.2147/JPR.S125556
                5317335
                ff09fe1c-d2b8-4016-86a1-7fe1d635f5c0
                © 2017 Yamada 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.

                History
                Categories
                Original Research

                Anesthesiology & Pain management
                sex characteristics,early-life adversity,chronic pain,somatoform disorders,disaster

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