Unveiling the relationship between central parkinsonian pain and motor symptoms in Parkinson's disease

Vila‐Chã, Nuno; Cavaco, Sara; Mendes, Alexandre; Gonçalves, Alexandra; Moreira, Inês; Fernandes, Joana; Damásio, Joana; Azevedo, Luís Filipe; Castro-Lopes, José Manuel

doi:10.1002/ejp.1413

Cited by 9 publications

(7 citation statements)

References 50 publications

(78 reference statements)

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“…Presence of motor fluctuations was also more frequent among patients with sleep disturbances. Previous studies have demonstrated that motor fluctuations are more common in PD patients who report pain 34–36. This pattern of findings raises the possibility that motor fluctuations may have a modulating effect on the relationship between pain and sleep.…”

Section: Discussionmentioning

confidence: 79%

<p>Sleep disturbances in Parkinson’s disease are associated with central parkinsonian pain</p>

Vila‐Chã¹,

Cavaco²,

Mendes³

et al. 2019

JPR

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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.

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Section: Discussionmentioning

confidence: 79%

<p>Sleep disturbances in Parkinson’s disease are associated with central parkinsonian pain</p>

Vila‐Chã¹,

Cavaco²,

Mendes³

et al. 2019

JPR

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“…Noteworthy cognition was assessed under the effects of antiparkinsonian medication. The central parkinsonian pain is believed to be related to a dopaminergic deficit, and there are reports of a greater relief of pain with antiparkinsonian medication than in other types of pain [ 7 , 8 ].…”

Section: Discussionmentioning

confidence: 99%

“…A cross-sectional study of PD patients was carried out in the Movement Disorders Clinic of Centro Hospitalar Universitário do Porto (CHUPorto). Full details of the protocol have been described in a previous article [ 7 ]. In brief, patients were eligible for inclusion if they met the United Kingdom Brain Bank criteria for diagnosis of PD [ 11 ].…”

Section: Methodsmentioning

confidence: 99%

“…Central parkinsonian pain is believed to be the only subtype of pain that is directly related to the disease itself and is the core feature of the putative Park pain subtype [ 6 ]. Patients with central parkinsonian pain are known to be younger, have earlier disease onset, fewer comorbidities, greater nonaxial motor symptom severity in on , more pain‐related disability, more sleep disturbances, and more relief of pain with antiparkinsonian medication than patients with non‐central parkinsonian pain [ 7 , 8 ]. It is also widely recognized that younger patients with PD usually have more preserved cognition and are at a higher risk of presenting impulse control disorders [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

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Central Pain in Parkinson’s Disease: Behavioral and Cognitive Characteristics

Vila‐Chã

Cavaco

Mendes

et al. 2021

Parkinson's Disease

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Introduction. Pain is a major nonmotor symptom of Parkinson’s disease (PD), and central parkinsonian pain is the core feature of the putative Park pain subtype of PD. This study aimed to explore the cognitive and behavioral profile of PD patients with central parkinsonian pain. Material and Methods. A structured interview was used to identify and characterize pain in a cohort of 260 consecutive PD patients. The Ford classification of pain was applied. The Dementia Rating Scale-2 (DRS-2) and the Impulse Control Disorders in Parkinson’s Disease Short Form (QUIP-S) were administered, and patients’ smoking habits were recorded. The Unified Parkinson’s Disease Rating Scale (UPDRS) was used to assess motor and nonmotor symptoms in off and on conditions. Results. One hundred and eighty-eight patients (68%) reported pain; and in 41 (22%) of them, the pain was classified as central parkinsonian pain. PD patients with central parkinsonian pain had better cognitive performance in DRS-2 Initiation/Perseveration and Conceptualization subscales but reported more other compulsive behaviors (e.g., hobbyism, punding, and walkabout) and had more current smoking habits than those without pain or with non-central parkinsonian pain. Multiple logistic regression analyses revealed that the DRS-2 Conceptualization subscale, other compulsive behaviors, and smoking habits remained statistically associated with central parkinsonian pain even when other significant covariates were considered. Only patients with pain, regardless of type, had a gambling disorder. Discussion. The study results provide further evidence that pain revealed that patients with central parkinsonian pain are more likely to present compulsive or addictive behaviors, despite having more preserved cognitive performance. Patients with central parkinsonian pain appear to have a distinct phenotype of PD.

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“…(Schrag et al, 2015). A few observational studies have shown that pain intensity ratings are associated with the severity of motor impairments and motor function scores (Allen et al, 2016; Vila-Cha et al, 2019), have a partial response to muscle-relaxing agents or cannabis (Balash et al, 2017; Lotan et al, 2014), and fluctuate in part with L-DOPA (Box 1) medication (Valkovic et al, 2015). PD pain is therefore often ascribed to muscle rigidity (Allen et al, 2016), but a recent large cohort study found that factors predicting overall pain included affective and autonomic symptoms, motor complications, female gender and younger age, but not motor impairment or disease duration (Silverdale et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Sensory neuropathy and nociception in rodent models of Parkinson's disease

Valek

Auburger

Tegeder

2019

Disease Models &Amp; Mechanisms

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Parkinson's disease (PD) often manifests with prodromal pain and sensory losses whose etiologies are not well understood. Multiple genetic and toxicity-based rodent models of PD partly recapitulate the histopathology and motor function deficits. Although far less studied, there is some evidence that rodents, similar to humans, develop sensory manifestations of the disease, which may precede motor disturbances and help to elucidate the underlying mechanisms of PD-associated pain at the molecular and neuron circuit levels. The present Review summarizes nociception and other sensory functions in frequently used rodent PD models within the context of the complex phenotypes. In terms of mechanisms, it appears that the acute loss of dopaminergic neurons in systemic toxicity models (MPTP, rotenone) primarily causes nociceptive hyperexcitability, presumably owing to a loss of inhibitory control, whereas genetic models primarily result in a progressive loss of heat perception, reflecting sensory fiber neuropathies. At the molecular level, neither α-synuclein deposits alone nor failure of mitophagy alone appear to be strong enough to result in axonal or synaptic pathology of nociceptive neurons that manifest at the behavioral level, and peripheral sensory loss may mask central ‘pain’ in behavioral tests. Hence, allostatic combinations or additional challenges and novel behavioral assessments are needed to better evaluate PD-associated sensory neuropathies and pain in rodents.

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Unveiling the relationship between central parkinsonian pain and motor symptoms in Parkinson's disease

Cited by 9 publications

References 50 publications

<p>Sleep disturbances in Parkinson’s disease are associated with central parkinsonian pain</p>

<p>Sleep disturbances in Parkinson’s disease are associated with central parkinsonian pain</p>

Central Pain in Parkinson’s Disease: Behavioral and Cognitive Characteristics

Sensory neuropathy and nociception in rodent models of Parkinson's disease

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