Parkinsonism and Related Disorders 18S1 (2012) S226–S228 Contents lists available at ScienceDirect Parkinsonism and Related Disorders journal homepage: www.elsevier.com/locate/parkreldis Pathophysiology of pain and fatigue in Parkinson’s disease A. Berardelli a,b, *, A. Conte a,b , G. Fabbrini a,b , M. Bologna b , A. Latorre a , L. Rocchi a , A. Suppa b a Department of Neurology and Psychiatry, “Sapienza” University of Rome, Rome, Italy b Neuromed I.R.C.C.S. Pozzilli (IS), Italy article info Keywords: Pain Fatigue Parkinson’s disease summary In Parkinson’s disease (PD), nigral degeneration determines an altered neuronal ouput from the subthalamic nucleus and globus pallidus, and as a consequence functional changes in the motor circuits linking basal ganglia to the motor cortical areas. Movement slowness, rigidity and tremor are among the principal motor symptoms of PD. Studies of movement execution have shown that PD patients have difficulty in performing simultaneous and sequential movements. In executing sequential movements the abnormalities of PD patients worsen as the sequence progresses. This phenomenon, called sequential effect, may be one of the mechanisms underlying the fatigue of PD patients. Cortical deafferentation is thought to be responsible for the motor disturbances of PD and studies using transcranial magnetic stimulation showed that in PD patients there are abnormalities in cortical plasticity and in cortical connectivity. Sensorimotor integration refers to the processes that link sensory input to motor output to produce appropriate voluntary movements. Sensory information is important for motor preparation and execution in parkinsonian patients, and PD patients have greater difficulty in performing movements when no external cues are provided. Investigating the role of sensory information, several studies provided evidence that PD patients have numerous somatosensory deficits, including tactile temporal discrimination threshold. Neurophysiological testing in PD has also found altered central somatosensory processing. Finally PD patients may experience painful sensations after the onset of the disease and various evidence suggests an abnormal nociceptive input processing in the central nervous system that might predispose PD patients to developing pain. © 2011 Elsevier Ltd. All rights reserved. 1. Introduction The functional organization of basal ganglia is characterized by several interconnected anatomical structures and multiple parallel networks. Motor input flows through basal ganglia and is driven via thalamus to the cortex, and also to brainstem and spinal cord. Motor symptoms in Parkinson’s disease are thought to be caused by degeneration of dopaminergic neurons in the substantia nigra pars compacta, secondarily leading to functional changes in the motor circuits connecting basal ganglia to the cortical motor areas. Motor abnormalities in PD are therefore considered the result of alterations in the cortico-striato-thalamo-cortical circuit [1]. 2. Fatigue in Parkinson’s disease In addition to motor symptoms, PD patients also have a number of non-motor symptoms including fatigue. Fatigue has been defined as an overwhelming sense of tiredness, lack of energy and feeling of exhaustion, and it is commonly divided in peripheral and central *Corresponding author. Prof. Alfredo Berardelli, Department of Neurology and Psychiatry, Viale dell’Universit` a, 30, 00185 Rome, Italy. Tel./fax: +39 0649914700. E-mail address: alfredo.berardelli@uniroma1.it (A. Berardelli). components [2]. Peripheral fatigue occurs when adequate force for a task can no longer be applied during repeated muscular contractions. Peripheral fatigue is frequently observed in several neurological diseases, including myasthenia gravis. Differently, patients with central fatigue have difficulty in initiating and sustaining mental and physical tasks in the absence of motor or physical impairment, and this is frequently observed in patients with chronic diseases including PD [2]. The reported prevalence of fatigue in PD ranges from 33% to 58%. Fatigue contributes directly and indirectly to restriction in activity and participation in daily activities (disablement) and is a major factor affecting quality of life. Although a number of studies have increasingly focused on the clinical aspects of fatigue inPD, the pathophysiology of fatigue is still largely unclear. To understand the pathophysiological mechanisms underlying central fatigue in PD, it is important to take into account possible relationships between central fatigue and other non-motor symptoms, including depression and apathy. Although depression and apathy are common symptoms in PD patients, the role of depression and apathy in determining fatigue in PD still remains controversial [2]. Another important aspect in the pathophysiology of central fatigue in PD is a possible relationship between fatigue and the high prevalence of sleep disturbances, including excessive 1353-8020/$ – see front matter © 2011 Elsevier Ltd. All rights reserved.