Neuroimaging Correlates of Pain in Parkinson's Disease: A Systematic Review of Structural and Resting-State fMRI Studies.

Chronic pain is a common non-motor symptom in Parkinson's disease (PD), but its central neural mechanisms are not fully understood. Structural and resting-state functional MRI offer non-invasive insights into brain structural and functional correlates of pain. This systematic review synthesizes neuroimaging evidence on the neural correlates of pain in PD. A search of PubMed, Scopus, Google Scholar, and Web of Science identified eight case-control studies, including 432 PD patients with pain (PDP), 225 without pain (PDNP), and 257 healthy controls (HCs). Structural MRI revealed prefrontal cortical thinning and reduced insular gyrification, while resting-state functional MRI showed altered activity and connectivity across basal ganglia, limbic, brainstem, sensorimotor, cerebellar, insula-temporo-parietal and parahippocampal networks. Key findings included reduced putamen activity negatively correlated with pain, disrupted striatal-limbic connectivity, and increased raphe nucleus connectivity positively associated with pain. Other alterations included impaired sensorimotor-cerebellar integration and amygdala hypoconnectivity linked to pain severity. Dopamine-responsive and dopamine-unresponsive pain phenotypes displayed distinct connectivity patterns. Compared to HCs, PDP exhibited reduced connectivity in pain-related networks. Dynamic connectivity of default mode and frontoparietal networks showed no consistent links with pain. Two studies employed multimodal imaging approaches. Findings converged with unimodal evidence implicating prefrontal, insular, orbitofrontal, cerebellar, and striato-limbic circuits. White matter abnormalities were observed versus HCs but not consistently between PDP and PDNP. Overall, the findings support a network-based pathophysiological framework for PD-related pain and highlight the need for multimodal, longitudinal, and mechanism- and dopaminergic response-specific investigations to clarify underlying mechanisms and inform targeted therapeutic strategies. REGISTRATION: Registered on the PROSPERO site on November 13, 2025 (ID: CRD420251230685). PERSPECTIVE: This review identifies notable structural and functional alterations in striatal, limbic, brainstem, and sensorimotor-cerebellar networks underlying pain in Parkinson's disease. These findings support a network-based framework for PD-related pain and highlight the need for multimodal, longitudinal, and pain subtype- and treatment response-specific studies to clarify mechanisms and guide targeted interventions.