Affiliations: [a] Department of Neurology, Medical Faculty Associates, George Washington University, Washington, DC, USA
| [b] Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
| [c] IRCCS Fondazione Santa Lucia, Rome, Italy
| [d] Department of Clinical Science and Translational Medicine, University of Rome Tor Vergata, Rome, Italy
| [e] King’s College London, Department of Neurosciences, Institute of Psychiatry, Psychology & Neuroscience, De Crespigny Park, London, United Kingdom
| [f] Parkinsons Foundation Centre of Excellence, King’s College Hospital, London, United Kingdom
Correspondence to: Antonio Pisani, MD, PhD, Department of Systems Medicine, University of Rome “Tor Vergata”, Via Montpellier 1, 00133 Rome, Italy. Tel.: +39 0672596010; Fax: +39 0672596006; E-mail: [email protected].
Note:  These authors contributed equally to this work
Abstract: Background:Pain is a disabling and often underestimated non-motor symptom (NMS) detrimentally affecting the quality of life of patients with Parkinson’s disease (PD). Objective:Here, we conducted a cross-sectional, observational international study on 167 patients with idiopathic PD in order to analyze the potential relationship between pain and other NMS. Methods:Subjects were assessed with the Unified Parkinson’s Disease Rating Scale (UPDRS) part III, Hoehn and Yahr (H&Y) stage, King’s Parkinson’s Disease Pain Scale (KPPS), Brief Pain Inventory (BPI), Non-Motor Symptoms Scale (NMSS), and Beck Depression Inventory (BDI). Spearman’s rank correlation coefficient, multiple regression and multiple index-based clustering algorithms were used for data analysis. Results:The prevalence of pain was 88.6%, was not correlated with age, motor severity (UPDRS part III) or disease duration, whereas a weak correlation with female gender and H&Y stage >2.5 was found. Multiple NMS correlated significantly with pain. Specifically, sleep disturbance had the strongest correlation with pain, followed by depression, gastrointestinal and cardiovascular disturbances. Further analyses showed that sleep and cardiovascular disturbance were independently associated with pain, and that these symptoms clustered together in a subset of PD patients. The relationship between pain, sleep and dysautonomia persisted independently from dopamine replacement therapy. Conclusion:Our study suggests that sleep disruption and cardiovascular disturbance are associated with pain in PD, and possibly identifies a specific subtype within PD patients with pain. Our data also indicate that sleep disruption, pain and dysautonomia may have a common pathophysiology, possibly involving non-dopaminergic pathways.