Identification of peripheral pain generators with sigma-1 receptor Positron Emission Tomography/Magnetic Resonance Imaging in complex regional pain syndrome: initial study in a prospective trial

Complex regional pain syndrome (CRPS) is a poorly understood chronic pain condition of the extremities presenting severe pain disproportionate to the causative injury. Owing to its heterogeneous clinical presentation and the lack of specific diagnostic tests, CRPS is often a diagnostic and therapeutic challenge. Early diagnosis and treatment of CRPS improve quality of life and delay disease progression. Identification of focal peripheral pain generators would provide an opportunity for targeted treatments with more limited side effects. A highly selective sigma-1 receptor positron emission tomography (PET) radioligand, [18F]FTC-146, has been developed and has shown promise in identifying inflammatory or nociceptive processes. Our aim was to investigate the utility of [18F]FTC-146 PET/MRI for identifying peripheral pain generators and assessing its impact on subsequent clinical management of patients with CRPS. This single-center study enrolled 15 subjects with a clinical diagnosis of CRPS to undergo [18F]FTC-146 PET/MRI. PET/MRI findings were reviewed and discussed with referring pain specialists. Pain scores and subsequent changes in pain management for each patient were prospectively noted. Potential pain generators were observed in 10 of 15 subjects. Subsequent pain treatments guided by abnormally increased foci of uptake on [18F]FTC-146 PET/MRI resulted in an average 5-point improvement in pain score in 80% (8/10) of subjects. Overall, [18F]FTC-146 PET/MRI was able to identify potential peripheral pain generators in the affected limbs of subjects with CRPS and subsequently guided targeted treatments that resulted in varying degrees of improvement in subjective pain scores.