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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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          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.


          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.


          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.


          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.

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          Most cited references 22

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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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              Collecting behavioural data using the world wide web: considerations for researchers.

              To identify and describe advantages, challenges, and ethical considerations of web based behavioural data collection. This discussion is based on the authors' experiences in survey development and study design, respondent recruitment, and internet research, and on the experiences of others as found in the literature. The advantages of using the world wide web to collect behavioural data include rapid access to numerous potential respondents and previously hidden populations, respondent openness and full participation, opportunities for student research, and reduced research costs. Challenges identified include issues related to sampling and sample representativeness, competition for the attention of respondents, and potential limitations resulting from the much cited "digital divide", literacy, and disability. Ethical considerations include anonymity and privacy, providing and substantiating informed consent, and potential risks of malfeasance. Computer mediated communications, including electronic mail, the world wide web, and interactive programs will play an ever increasing part in the future of behavioural science research. Justifiable concerns regarding the use of the world wide web in research exist, but as access to, and use of, the internet becomes more widely and representatively distributed globally, the world wide web will become more applicable. In fact, the world wide web may be the only research tool able to reach some previously hidden population subgroups. Furthermore, many of the criticisms of online data collection are common to other survey research methodologies.

                Author and article information

                J Pain Res
                J Pain Res
                Journal of Pain Research
                Journal of Pain Research
                Dove Medical Press
                16 February 2017
                : 10
                : 427-433
                [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
                © 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.

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