Differences in Brain Activity Between Dopa-Responsive and -Unresponsive Pain in Parkinson’s Disease

INTRODUCTION: Pain in Parkinson’s disease is poorly understood, and most patients with pain do not respond to dopaminergic drugs. We aimed to explore the mechanisms of dopa-responsive and -unresponsive pain by comparing such patients against patients without pain in terms of neural activity and functional connectivity in the brain. METHODS: We prospectively examined 31 Parkinson’s patients with dopa-responsive pain, 51 with dopa-unresponsive pain and 93 without pain using resting-state functional magnetic resonance imaging. Neural activity was assessed in terms of the amplitude of low-frequency fluctuation, while functional connectivity was assessed based on analysis of regions of interest. RESULTS: Patients with dopa-unresponsive pain showed significantly higher amplitude of low-frequency fluctuation in the right parahippocampal/lingual region than patients with no pain. However, there was no amplitude difference between the dopa-responsive pain group and the no pain group. Patients with dopa-unresponsive pain also differed significantly from patients with no pain in their functional connections between the superior temporal gyrus and other areas of cerebral cortex, between amygdala and thalamus and between the amygdala and putamen. Patients with dopa-responsive pain differed significantly from patients with no pain in their functional connections between temporal fusiform cortex and cerebellum, between precentral gyrus and temporal fusiform cortex and between precentral gyrus and cerebellum. CONCLUSIONS: Regional neural activity and functional connectivity in the brain differ substantially among Parkinson’s patients with dopa-unresponsive pain, dopa-responsive pain or no pain. Our results suggest that dopa-responsive and -unresponsive pain may arise through different mechanisms, which may help guide the development of targeted therapies.