Imaging Primary Chronic Pain Syndromes: Current Evidence, Clinical Relevance, and Advances in MRI and PET/CT

Primary chronic pain syndromes are increasingly understood through advanced neuroimaging techniques, which reveal consistent structural, functional, and molecular alterations in the central nervous system. Multi-modal Magnetic Resonance Imaging-including diffusion, structural, and functional approaches-demonstrates reduced gray matter, disrupted neural network connectivity, and altered activation in key pain-processing regions such as the insula, thalamus, and anterior cingulate cortex, with distinct patterns for pain anticipation and stimulus processing. Positron emission tomography/CT imaging further elucidates neurobiological mechanisms, identifying changes in glucose metabolism, neurotransmitter systems, and neuroinflammation, particularly through elevated Translocator Protein (marker of microglial activation) signals and altered opioid and dopaminergic pathways in chronic pain populations. Recent studies highlight the potential of imaging biomarkers for diagnosis, patient stratification, and prediction of treatment response, with machine learning and multivariate pattern analysis improving specificity and classification accuracy. Integrating imaging, molecular, and psychosocial data enables the creation of composite signatures for personalized pain management. Despite these advances, challenges remain in standardizing imaging, validating biomarkers, and implementing findings into routine clinical practice. Ongoing research for imaging pain syndromes focuses on harmonization efforts, large-scale multicenter collaborations, and the integration of artificial intelligence to optimize biomarker utilization and strengthen clinical decision-support systems. This review explores how advanced Magnetic Resonance Imaging and Positron emission tomography/CT techniques have transformed the understanding of primary chronic pain syndromes, facilitating precision diagnosis and targeted therapeutic strategies.