Pain in early-stage Parkinson's disease: Implications from clinical features to pathophysiology mechanisms

Pain is a common non-motor symptom of Parkinson's disease (PD) that markedly impacts patients' quality of life. Although pain occurs mostly secondary to motor disability of PD, pain may antedate motor symptoms by years. Numerous studies have shown that PD patients manifest altered sensory and pain thresholds compared with control subjects. Although both levodopa and deep brain stimulation improve motor symptoms, there remains no direct correlation between motor improvement and altered pain sensitivity, suggesting that motor symptoms and pain do not necessarily share pathogenetic mechanisms. Whether nociceptive processing is dysfunctional in the early stages of PD, when motor symptoms are not prominent, remains uncertain. In this review, we highlight the evidence for disrupted nociceptive processing in patients with early-stage PD. Painful symptoms and aberrant pain processing in early PD are associated with both central and peripheral deafferentation. Dopamine depletion in selective striatal regions, and the development of Lewy pathology in specific non-dopaminergic subcortical areas, underlie the clinical features of pain at this early disease stage. An increased awareness of pain as an early feature of PD might provide further insights into a mechanism-based approach to sensory system dysregulation in this disease.