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      The Association of Depression and Anxiety with Pain: A Study from NESDA


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          Chronic pain is commonly co-morbid with a depressive or anxiety disorder. Objective of this study is to examine the influence of depression, along with anxiety, on pain-related disability, pain intensity, and pain location in a large sample of adults with and without a depressive and/or anxiety disorder. The study population consisted of 2981 participants with a depressive, anxiety, co-morbid depressive and anxiety disorder, remitted disorder or no current disorder (controls). Severity of depressive and anxiety symptoms was also assessed. In separate multinomial regression analyses, the association of presence of depressive or anxiety disorders and symptom severity with the Chronic Pain Grade and location of pain was explored. Presence of a depressive (OR = 6.67; P<.001), anxiety (OR = 4.84; P<.001), or co-morbid depressive and anxiety disorder (OR = 30.26; P<.001) was associated with the Chronic Pain Grade. Moreover, symptom severity was associated with more disabling and severely limiting pain. Also, a remitted depressive or anxiety disorder showed more disabling and severely limiting pain (OR = 3.53; P<.001) as compared to controls. A current anxiety disorder (OR = 2.96; p<.001) and a co-morbid depressive and anxiety disorder (OR = 5.15; P<.001) were more strongly associated with cardio-respiratory pain, than gastro-intestinal or musculoskeletal pain. These findings remain after adjustment for chronic cardio respiratory illness. Patients with a current and remitted depressive and/or anxiety disorder and those with more severe symptoms have more disabling pain and pain of cardio-respiratory nature, than persons without a depressive or anxiety disorder. This warrants further research.

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          Descending control of pain.

          Upon receipt in the dorsal horn (DH) of the spinal cord, nociceptive (pain-signalling) information from the viscera, skin and other organs is subject to extensive processing by a diversity of mechanisms, certain of which enhance, and certain of which inhibit, its transfer to higher centres. In this regard, a network of descending pathways projecting from cerebral structures to the DH plays a complex and crucial role. Specific centrifugal pathways either suppress (descending inhibition) or potentiate (descending facilitation) passage of nociceptive messages to the brain. Engagement of descending inhibition by the opioid analgesic, morphine, fulfils an important role in its pain-relieving properties, while induction of analgesia by the adrenergic agonist, clonidine, reflects actions at alpha(2)-adrenoceptors (alpha(2)-ARs) in the DH normally recruited by descending pathways. However, opioids and adrenergic agents exploit but a tiny fraction of the vast panoply of mechanisms now known to be involved in the induction and/or expression of descending controls. For example, no drug interfering with descending facilitation is currently available for clinical use. The present review focuses on: (1) the organisation of descending pathways and their pathophysiological significance; (2) the role of individual transmitters and specific receptor types in the modulation and expression of mechanisms of descending inhibition and facilitation and (3) the advantages and limitations of established and innovative analgesic strategies which act by manipulation of descending controls. Knowledge of descending pathways has increased exponentially in recent years, so this is an opportune moment to survey their operation and therapeutic relevance to the improved management of pain.
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            The Inventory of Depressive Symptomatology (IDS): psychometric properties.

            The psychometric properties of the 28- and 30-item versions of the Inventory of Depressive Symptomatology, Clinician-Rated (IDS-C) and Self-Report (IDS-SR) are reported in a total of 434 (28-item) and 337 (30-item) adult out-patients with current major depressive disorder and 118 adult euthymic subjects (15 remitted depressed and 103 normal controls). Cronbach's alpha ranged from 0.92 to 0.94 for the total sample and from 0.76 to 0.82 for those with current depression. Item total correlations, as well as several tests of concurrent and discriminant validity are reported. Factor analysis revealed three dimensions (cognitive/mood, anxiety/arousal and vegetative) for each scale. Analysis of sensitivity to change in symptom severity in an open-label trial of fluoxetine (N = 58) showed that the IDS-C and IDS-SR were highly related to the 17-item Hamilton Rating Scale for Depression. Given the more complete item coverage, satisfactory psychometric properties, and high correlations with the above standard ratings, the 30-item IDS-C and IDS-SR can be used to evaluate depressive symptom severity. The availability of similar item content for clinician-rated and self-reported versions allows more direct evaluations of these two perspectives.
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              Grading the severity of chronic pain.

              This research develops and evaluates a simple method of grading the severity of chronic pain for use in general population surveys and studies of primary care pain patients. Measures of pain intensity, disability, persistence and recency of onset were tested for their ability to grade chronic pain severity in a longitudinal study of primary care back pain (n = 1213), headache (n = 779) and temporomandibular disorder pain (n = 397) patients. A Guttman scale analysis showed that pain intensity and disability measures formed a reliable hierarchical scale. Pain intensity measures appeared to scale the lower range of global severity while disability measures appeared to scale the upper range of global severity. Recency of onset and days in pain in the prior 6 months did not scale with pain intensity or disability. Using simple scoring rules, pain severity was graded into 4 hierarchical classes: Grade I, low disability--low intensity; Grade II, low disability--high intensity; Grade III, high disability--moderately limiting; and Grade IV, high disability--severely limiting. For each pain site, Chronic Pain Grade measured at baseline showed a highly statistically significant and monotonically increasing relationship with unemployment rate, pain-related functional limitations, depression, fair to poor self-rated health, frequent use of opioid analgesics, and frequent pain-related doctor visits both at baseline and at 1-year follow-up. Days in Pain was related to these variables, but not as strongly as Chronic Pain Grade. Recent onset cases (first onset within the prior 3 months) did not show differences in psychological and behavioral dysfunction when compared to persons with less recent onset. Using longitudinal data from a population-based study (n = 803), Chronic Pain Grade at baseline predicted the presence of pain in the prior 2 weeks. Chronic Pain Grade and pain-related functional limitations at 3-year follow-up. Grading chronic pain as a function of pain intensity and pain-related disability may be useful when a brief ordinal measure of global pain severity is required. Pain persistence, measured by days in pain in a fixed time period, provides useful additional information.

                Author and article information

                Role: Editor
                PLoS One
                PLoS ONE
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                15 October 2014
                : 9
                : 10
                [1 ]TopClinical Center for Body, Mind, and Health, GGz Breburg Tilburg, Tilburg, The Netherlands
                [2 ]Tilburg School of Behavioral and Social Sciences, Tranzo Department, University of Tilburg, Tilburg, The Netherlands
                [3 ]Department of Psychiatry, EMGO Institute for Health and Care research, VU University Medical Centre, Amsterdam, The Netherlands
                [4 ]GGZ inGeest, Mental Health Institute, Amsterdam, The Netherlands
                [5 ]Arkin, Mental Health Institute, Amsterdam, The Netherlands
                [6 ]Department of Clinical Psychology, VU University, Amsterdam, The Netherlands
                [7 ]Department of General Practice, EMGO Institute for Health and Care Research, VU University Medical Centre, Amsterdam, The Netherlands
                [8 ]Department of Public Health and Primary Care, Leiden university Medical Centre, Leiden, The Netherlands
                [9 ]Institute of Psychology, Leiden University, Leiden, The Netherlands
                [10 ]Department of Psychiatry, Leiden University Medical Centre, Leiden, The Netherlands
                [11 ]Trimbos Institute, Utrecht, the Netherlands
                National Cheng Kung University Medical College, Taiwan
                Author notes

                Competing Interests: The authors of this manuscript have read the journal's policy and have the following competing interests: ATFB reports grants from Eli Lilly, grants from Astra Zeneca, grants from Jansen, grants from Shire, personal fees (as a speaker) from Eli Lilly, and personal fees (as a speaker) from Lundbeck, outside the submitted work. JD and CMFC report grants from Eli Lilly, outside the submitted work. BWJHP reports grants from Dutch government, ministry of Health (ZonMw), during the conduct of the study. This does not alter their adherence to PLOS ONE policies on sharing data and materials, except those mentioned in the data availability statement.

                Conceived and designed the experiments: BWJHP ATFB PS HWJM. Performed the experiments: BWJHP ATFB PS HWJM. Analyzed the data: EH MMJGG BWJHP HWJM MWMW PS. Contributed reagents/materials/analysis tools: BWJHP ATFB PS HWJM. Contributed to the writing of the manuscript: EH MMJGG ATFB JD BWJHP HWJM MWMW PS CMFC.


                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                Page count
                Pages: 11
                The infrastructure for the NESDA study is funded through the Geestkracht program of the Netherlands Organisation for Health Research and Development (Zon-MW, grant number 10-000-1002) and is supported by participating universities and mental health care organisations (VU University Medical Center, GGZ inGeest, Arkin, Leiden University Medical Center, GGZ Rivierduinen, University Medical Center Groningen, Lentis, GGZ Friesland, GGZ Drenthe, IQ Healthcare, Netherlands Institute for Health Services Research [NIVEL], and the Netherlands Institute of Mental Health and Addiction [Trimbos]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Research Article
                Biology and Life Sciences
                Pain Psychology
                Medicine and Health Sciences
                Mental Health and Psychiatry
                Mood Disorders
                Neuropsychiatric Disorders
                Anxiety Disorders
                Pain Management
                Abdominal Pain
                Rheumatic Pain
                Pathology and Laboratory Medicine
                Signs and Symptoms
                Research and Analysis Methods
                Research Design
                Cohort Studies
                Observational Studies
                Social Sciences
                Custom metadata
                The authors confirm that, for approved reasons, some access restrictions apply to the data underlying the findings. Researchers can submit a research plan, which describes the background en methods of a proposed research question, and a request for specific data of the NESDA database to answer the research question. Information about NESDA data can be requested by contacting the principal investigator of NESDA: Prof. Dr. Brenda Penninx: b.penninx@ 123456vumc.nl .



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