Pain and sensory abnormalities in prodromal and early Parkinson's disease: mechanisms, assessment, and clinical implications.

Research overview

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Parkinson's disease (PD) is traditionally characterized by motor symptoms; however, non-motor symptoms, particularly pain and sensory disturbances, are increasingly recognized as potential early manifestations that precede motor onset. Pain has been reported in up to 59% of patients before the onset of motor symptoms and in up to 72% in the early stages of PD, yet its underlying mechanisms and clinical implications remain insufficiently understood. Emerging evidence suggests that dopaminergic dysfunction may alter nociceptive processing across both peripheral and central pathways, involving changes within spinal, brainstem, and cortical pain networks. Despite this, the heterogeneity of pain phenotypes and the lack of standardized assessment approaches continue to limit the diagnostic and clinical utility of pain as an early disease indicator. Importantly, early pain symptoms may lead to misinterpretation and unnecessary investigations, potentially delaying PD diagnosis. This narrative review critically examines four key aspects of pain in prodromal to early-stage PD: (1) pain as an early clinical feature, (2) underlying nociceptive and neurodegenerative mechanisms, (3) alterations in small-fiber function assessed by quantitative sensory testing, and (4) large-fiber involvement evaluated through nerve conduction studies. By integrating current evidence, this review highlights the role of pain as a potential early indicator of PD, synthesizes current knowledge on sensory dysfunction across the prodromal to early disease spectrum, and identifies key gaps to support diagnosis, improved patient stratification, and mechanism-based management strategies.

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