Altered functional activity and connectivity in Parkinson's disease with chronic pain: a resting-state fMRI study

Background Chronic pain is a common non-motor symptom of Parkinson's disease (PD) that significantly impacts patients' quality of life, but its neural mechanisms remain poorly understood. This study investigated changes in spontaneous neuronal activity and functional connectivity (FC) associated with chronic pain in PD patients.Methods The study included 41 PD patients with chronic pain (PDP), 41 PD patients without pain (nPDP), and 29 healthy controls. Pain severity was assessed using the visual analog scale (VAS). Resting-state fMRI images were used to measure the amplitude of low-frequency fluctuations (ALFF) as an indicator of regional brain activity. Subsequently, FC analysis was performed to evaluate synchronization between ALFF-identified regions and the entire brain.Results Compared to nPDP patients, PDP patients exhibited decreased ALFF in the right putamen, and increased ALFF in motor regions, including the right superior frontal gyrus/supplementary motor area and the left paracentral lobule/primary motor cortex. Additionally, PDP patients exhibited diminished right putamen-based FC in the midbrain, anterior cingulate cortex, orbitofrontal cortex, middle frontal gyrus, middle temporal gyrus, and posterior cerebellar lobe. The correlation analysis revealed that ALFF values in the right putamen were negatively associated with VAS scores in PDP patients.Conclusion This study demonstrates that chronic pain in PD is associated with reduced ALFF in the putamen and disrupted FC with brain regions involved in pain perception and modulation, highlighting the critical role of dopaminergic degeneration in the development and maintenance of pain in PD.