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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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      Commentary: Novel Use of Offset Analgesia to Assess Adolescents and Adults with Treatment Resistant Endometriosis-Associated Pain

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          Abstract

          Background and Objective

          Endometriosis, affecting approximately 176 million adults and adolescents worldwide, is a debilitating condition in which uterine tissue grows outside the uterus. The condition costs the US economy approximately $78 billion annually in pain-related disability. By understanding the neural underpinnings of endometriosis-associated pain (EAP) and risk factors for chronification, translational research methods could lessen diagnostic delays and maximize successful pain remediation. This can be accomplished by the novel use of a known method, offset analgesia (OA), to better elucidate the neural mechanisms that may contribute to and maintain EAP. This commentary will provide justification and rationale for the use of OA in the study of EAP.

          Conclusion

          Utilizing an OA paradigm in patients with endometriosis, especially adolescents, may (1) provide insight into neural mechanisms contributing to pain maintenance, which could capture those at-risk for the transition to chronic pelvic pain, (2) provide a metric for the development of future centrally mediated treatment options for this population, and (3) elucidate the brain changes that result in resistance to treatment and pain chronification.

          Most cited references50

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          Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): standardized protocol and reference values.

          The nationwide multicenter trials of the German Research Network on Neuropathic Pain (DFNS) aim to characterize the somatosensory phenotype of patients with neuropathic pain. For this purpose, we have implemented a standardized quantitative sensory testing (QST) protocol giving a complete profile for one region within 30 min. To judge plus or minus signs in patients we have now established age- and gender-matched absolute and relative QST reference values from 180 healthy subjects, assessed bilaterally over face, hand and foot. We determined thermal detection and pain thresholds including a test for paradoxical heat sensations, mechanical detection thresholds to von Frey filaments and a 64 Hz tuning fork, mechanical pain thresholds to pinprick stimuli and blunt pressure, stimulus/response-functions for pinprick and dynamic mechanical allodynia, and pain summation (wind-up ratio). QST parameters were region specific and age dependent. Pain thresholds were significantly lower in women than men. Detection thresholds were generally independent of gender. Reference data were normalized to the specific group means and variances (region, age, gender) by calculating z-scores. Due to confidence limits close to the respective limits of the possible data range, heat hypoalgesia, cold hypoalgesia, and mechanical hyperesthesia can hardly be diagnosed. Nevertheless, these parameters can be used for group comparisons. Sensitivity is enhanced by side-to-side comparisons by a factor ranging from 1.1 to 2.5. Relative comparisons across body regions do not offer advantages over absolute reference values. Application of this standardized QST protocol in patients and human surrogate models will allow to infer underlying mechanisms from somatosensory phenotypes.
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            The burden of endometriosis: costs and quality of life of women with endometriosis and treated in referral centres.

            This study aimed to calculate costs and health-related quality of life of women with endometriosis-associated symptoms treated in referral centres. A prospective, multi-centre, questionnaire-based survey measured costs and quality of life in ambulatory care and in 12 tertiary care centres in 10 countries. The study enrolled women with a diagnosis of endometriosis and with at least one centre-specific contact related to endometriosis-associated symptoms in 2008. The main outcome measures were health care costs, costs of productivity loss, total costs and quality-adjusted life years. Predictors of costs were identified using regression analysis. Data analysis of 909 women demonstrated that the average annual total cost per woman was €9579 (95% confidence interval €8559-€10 599). Costs of productivity loss of €6298 per woman were double the health care costs of €3113 per woman. Health care costs were mainly due to surgery (29%), monitoring tests (19%) and hospitalization (18%) and physician visits (16%). Endometriosis-associated symptoms generated 0.809 quality-adjusted life years per woman. Decreased quality of life was the most important predictor of direct health care and total costs. Costs were greater with increasing severity of endometriosis, presence of pelvic pain, presence of infertility and a higher number of years since diagnosis. Our study invited women to report resource use based on endometriosis-associated symptoms only, rather than drawing on a control population of women without endometriosis. Our study showed that the economic burden associated with endometriosis treated in referral centres is high and is similar to other chronic diseases (diabetes, Crohn's disease, rheumatoid arthritis). It arises predominantly from productivity loss, and is predicted by decreased quality of life.
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              The pains of endometriosis.

              Endometriosis is a disease defined by the presence of endometrial tissue outside of the uterus. Severe pelvic pain is often associated with endometriosis, and this pain can be diminished with therapies that suppress estrogen production. Many women with endometriosis also suffer from other chronic pain conditions. Recent studies suggest that mechanisms underlying these pains and sensitivity to estrogen involve the growth into the ectopic endometrial tissue of a nerve supply, which could have a varied and widespread influence on the activity of neurons throughout the central nervous system.
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                Author and article information

                Journal
                J Pain Res
                J Pain Res
                jpr
                jpainres
                Journal of Pain Research
                Dove
                1178-7090
                02 November 2020
                2020
                : 13
                : 2775-2782
                Affiliations
                [1 ]Center for Pain and the Brain (P.A.I.N. Group), Department of Anesthesiology, Critical Care, and Pain Medicine, Boston Children’s Hospital , Boston, MA, USA
                [2 ]Biobehavioral Pediatric Pain Lab, Department of Psychiatry and Behavioral Sciences, Boston Children’s Hospital , Boston, MA, USA
                [3 ]Nuffield Department of Women’s and Reproductive Health, Medical Sciences Division, University of Oxford , Oxford, Oxfordshire, UK
                [4 ]Department of Anesthesiology, Harvard Medical School , Boston, MA, USA
                [5 ]Department of Psychiatry, Harvard Medical School , Boston, MA, USA
                Author notes
                Correspondence: Christine B Sieberg Biobehavioral Pediatric Pain Lab, Department of Psychiatry and Behavioral Sciences, Boston Children’s Hospital , 21 Autumn St, Boston, MA, USATel +1 617-355-2296 Email christine.sieberg@childrens.harvard.edu
                [*]

                These authors contributed equally to this work

                Author information
                http://orcid.org/0000-0003-1696-0340
                Article
                276135
                10.2147/JPR.S276135
                7660453
                f478347c-48eb-4249-9c1d-e13263988b02
                © 2020 Lunde 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
                : 08 August 2020
                : 10 October 2020
                Page count
                Figures: 1, References: 50, Pages: 8
                Funding
                Funded by: United States Department of Defense, open-funder-registry 10.13039/100000005;
                Funded by: K23 Career Development;
                CBS and DB are Partnering PIs on a Peer Review Medical Research Program Investigator-Initiated Research Award from the United States Department of Defense (W81XWH19105060); CBS is also funded by a K23 Career Development Award from NIH (GM123372).
                Categories
                Commentary

                Anesthesiology & Pain management
                endometriosis,chronic pain,offset analgesia,central nervous system

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