The central neurometabolic fingerprint of persistent spinal pain syndrome type 2: A prospective [18F]FDG PET/CT neuroimaging study

Persistent spinal pain syndrome type 2 (PSPS-T2) is a disabling pain condition that persists after spinal surgery. While spinal cord stimulation (SCS) offers symptomatic relief, objective biomarkers to guide diagnosis and treatment are lacking. In this prospective cohort study, fifteen PSPS-T2 patients underwent dedicated [ 18 F]FDG PET/CT brain imaging prior to SCS implantation. Group-level metabolic patterns were compared to matched healthy controls using statistical parametric mapping. Regional metabolism was correlated with pain scores and neurotransmitter PET atlases using JuSpace. PSPS-T2 patients exhibited a distributed pattern of altered glucose metabolism involving frontal, temporal and cerebellar regions. Significant hypermetabolism was observed in the left temporal pole, right inferior temporal gyrus, and bilateral cerebellar lobule VIII, whereas hypometabolism was identified in the right fusiform gyrus, right superior frontal gyrus, left gyrus rectus, and cerebellar vermis. Moreover, there were significant spatial correlations between these metabolic changes and serotonergic and glutamatergic neurotransmitter systems. Furthermore, higher baseline pain was associated with increased frontal and temporal metabolism, whereas post-intervention pain was negatively correlated with metabolism in the temporal pole. These findings suggests that PSPS-T2 is characterized by network-level alterations in brain regions integrating sensory, emotional, and cognitive aspects of pain, with a neurochemical signature implicating serotonergic and glutamatergic systems. Although preliminary, this works provides evidence for a disease-relevant neurometabolic profile and highlights the potential of [ 18 F]FDG PET/CT for investigating central pain mechanisms. Future research should focus on validating this marker in larger populations.