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      Journal of Pain Research (submit here)

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      Sleep disturbances in Parkinson’s disease are associated with central parkinsonian pain

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          Abstract

          Introduction

          Sleep disturbances and pain are common non-motor symptoms in Parkinson’s disease (PD). This study aimed to explore the association between these two symptoms in a cohort of patients with PD.

          Materials and methods

          The Parkinson’s Disease Sleep Scale (PDSS-2) was used to identify sleep disturbances in a series of 229 PD patients. The identification and characterization of pain was performed by a semi-structured interview and by the application of the Ford classification and the Brief Pain Inventory (BPI). The Unified Parkinson’s Disease Rating Scale-III, Hoehn & Yahr (H&Y), and Schwab and England Independence Scale were used to assess motor symptoms and functional independence in off and on conditions. The Hospital Anxiety and Depression Scale (HADS) and SF-36 were applied to screen for anxiety and depression and to evaluate the quality of life. Non-parametric tests were used for group comparisons and logistic regressions were applied to explore predictors of sleep disturbances.

          Results

          Seventy-five (33%) patients had clinically relevant sleep disturbances (PDSS-2≥18) and 162 patients (71%) reported pain. Of those with pain, 38 (24%) had central parkinsonian pain. PD patients with sleep disturbances experienced more pain and had more severe motor symptoms, lower functional independence, more anxiety and depression symptoms, and worst quality of life. Among patients with pain, central parkinsonian pain was the subtype of pain with the highest odds of sleep disturbances, even when taking into account motor symptoms (H&Y off), motor fluctuations, intensity of pain (BPI), and symptoms of anxiety and depression (HADS).

          Conclusions

          The association between pain and sleep disturbances in PD appears to be dependent on subtype of pain. The close relationship between central parkinsonian pain and sleep disturbances in PD raises the possibility of common pathophysiological mechanisms. A better understanding of the relationship between sleep disturbances and central parkinsonian pain may contribute to the development of new care strategies in PD patients.

          Most cited references33

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          Sleep deprivation and pain perception.

          Chronically painful conditions are frequently associated with sleep disturbances, i.e. changes in sleep continuity and sleep architecture as well as increased sleepiness during daytime. A new hypothesis, which has attracted more and more attention, is that disturbances of sleep cause or modulate acute and chronic pain. Since it is well-known that pain disturbs sleep the relationship between the two has since recently been seen as reciprocal. To fathom the causal direction from sleep to pain we have reviewed experimental human and animal studies on the effects of sleep deprivation on pain processing. According to the majority of the studies, sleep deprivation produces hyperalgesic changes. Furthermore, sleep deprivation can interfere with analgesic treatments involving opioidergic and serotoninergic mechanisms of action. The still existing inconsistency of the human data and the exclusive focus on REM sleep deprivation in animals so far do not allow us to draw firm conclusions as to whether the hyperalgesic effects are due to the deprivation of specific sleep stages or whether they result from a generalized disruption of sleep continuity.
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            Parkinson's disease sleep scale--validation of the revised version PDSS-2.

            The previous Parkinson's disease sleep scale (PDSS) is a 15-item visual analogue scale that assesses the profile of nocturnal disturbances in Parkinson's disease (PD) patients. To extend the scale so that it becomes a frequency measure scale with five categories and encompasses unmet needs such as restless legs syndrome, akinesia, pain, and sleep apnea. For validation of the PDSS-2, PD patients' ratings and investigators' interviews were compared to ratings from a semistructured interview with a caregiver/partner, and to related scales. PDSS-2 was repeated for test-retest-reliability after 1-3 days. A total of 113 PD patients showed a mean (SD) total score of 16.5 (±8.9) (range: 2-40) indicating mild to moderate sleep disturbances. PDSS-2 item-total correlation for proving internal consistency was satisfactory (correlations >0.30). From a factor analysis, three subscales were derived: (1) "motor problems at night," (2) "PD symptoms at night" and (3) "disturbed sleep." The alpha coefficient for the total score was 0.73, for subscales 0.47 to 0.66. The test-retest-reliability intra-class-coefficient for the total score was 0.80, with 0.69 and 0.77 within the subscales. For discriminative validity, significant differences were found in the PDSS-2 total score depending on CGI and Hoehn and Yahr severity levels. A comparison between caregivers' and patients' ratings was carried out. The PDSS-2, with an extended spectrum of nocturnal disabilities and easier use for patients, is a reliable, valid, precise, and potentially treatment-responsive tool for measuring sleep disorders in PD. Copyright © 2011 Movement Disorder Society.
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              Identification of wake-active dopaminergic neurons in the ventral periaqueductal gray matter.

              Recent evidence suggests that dopamine plays an important role in arousal, but the location of the dopaminergic neurons that may regulate arousal remains unclear. It is sometimes assumed that the dopaminergic neurons in the ventral tegmental area that project to the prefrontal cortex and striatum may regulate the state of arousal; however, the firing of these dopaminergic neurons does not correlate with overall levels of behavioral wakefulness. We identified wake-active dopaminergic neurons by combining immunohistochemical staining for Fos and tyrosine hydroxylase (TH) in awake and sleeping rats. Approximately 50% of the TH-immunoreactive (TH-ir) cells in the ventral periaqueductal gray matter (vPAG) expressed Fos protein during natural wakefulness or wakefulness induced by environmental stimulation, but none expressed Fos during sleep. Fos immunoreactivity was not seen in the substantia nigra TH-immunoreactive cells in either condition. Injections of 6-hydroxydopamine into the vPAG, which killed 55-65% of wake-active TH-ir cells but did not injure nearby serotoninergic cells, increased total daily sleep by approximately 20%. By combining retrograde and anterograde tracing, we showed that these wake-active dopaminergic cells have extensive reciprocal connections with the sleep-wake regulatory system. The vPAG dopaminergic cells may provide the long-sought ascending dopaminergic waking influence. In addition, their close relationship with the dorsal raphe nucleus will require reassessment of previous studies of the role of the dorsal raphe nucleus in sleep, because many of those experiments may have been confounded by the then-unrecognized presence of intermingled wake-active dopaminergic neurons.
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                Author and article information

                Journal
                J Pain Res
                J Pain Res
                JPR
                jpainres
                Journal of Pain Research
                Dove
                1178-7090
                12 July 2019
                2019
                : 12
                : 2137-2144
                Affiliations
                [1 ]Department of Neurology, Centro Hospitalar do Porto , Porto, Portugal
                [2 ]Laboratory of Neurobiology of Human Behavior, Centro Hospitalar do Porto , Porto, Portugal
                [3 ]Unity in Multidisciplinary Research on Biomedicine (UMIB), Abel Salazar Biomedical Sciences Institute, University of Porto , Porto, Portugal
                [4 ]Centre for Health Technology and Services Research (CINTESIS), University of Porto , Porto, Portugal
                [5 ]Institute for Molecular and Cell Biology (IBMC), University of Porto , Porto, Portugal
                [6 ]National Observatory for Pain – NOPain, Faculty of Medicine, University of Porto , Porto, Portugal
                [7 ]Department of Community Medicine, Information and Health Decision Sciences (MEDCIDS), Faculty of Medicine, University of Porto , Porto, Portugal
                [8 ]Department of Biomedicine, Faculty of Medicine, University of Porto , Porto, Portugal
                Author notes
                Correspondence: N Vila-ChãServiço de Neurologia, Hospital de Santo António, Centro Hospitalar do Porto , Largo Prof. Abel Salazar, 4099-001Porto, PortugalTel +351 22 207 7500Email nunovilacha@ 123456hotmail.com
                Article
                206182
                10.2147/JPR.S206182
                6635894
                b39066d5-2fff-4a02-9961-aa39d5589cf5
                © 2019 Vila-Chã 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
                : 20 February 2019
                : 17 June 2019
                Page count
                Figures: 1, Tables: 2, References: 48, Pages: 8
                Categories
                Original Research

                Anesthesiology & Pain management
                parkinson’s disease,sleep disturbances,central parkinsonian pain

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