Pain mechanisms in PsA: differentiating inflammation-related pain in Achilles enthesitis using US and functional MRI

Abstract Objectives Pain in PsA is common and multifactorial, involving nociceptive, neuropathic and nociplastic mechanisms. We hypothesized that PsA patients with entheseal pain exhibit distinct brain activation patterns on functional MRI (fMRI), depending on the presence of US-detected inflammation. Methods PsA patients underwent clinical evaluation, US assessment of the Achilles tendon and fMRI brain imaging. Participants were grouped as follows: Group 1—clinical Achilles enthesitis with active US findings (hypoechogenicity and Doppler ≥grade-2); Group 2—clinical enthesitis but negative US; Group 3—no clinical or US evidence of enthesitis. The primary comparison (Groups 1 vs 2) evaluated whether US-confirmed inflammation is associated with distinct fMRI patterns. The secondary comparison (Groups 1 vs 3) aimed to distinguish inflammation-specific responses from general disease-related changes. Results Sixteen PsA patients were included. Group 1 showed significantly higher activation in brain regions involved in pain modulation, cognitive processing and attention compared with Group 2 [(middle frontal gyrus T-score: 6.92, P-value: 0.009), (inferior triangularis T-score: 4.53, P-value: 0.009), (inferior parietal lobule triangularis T-score: 5.94, P-value: 0.015), (supramarginal gyrus T-score: 5.28, P-value: 0.015), (superior medial FG T-score: 4.88, P-value: 0.022)]. Regarding comparison for pain-positive vs pain-negative patients, Group 1 had more activity than Group 3 in the supramarginal gyrus and inferior parietal lobule. Conclusion US-detected entheseal inflammation may be associated with distinct central pain-processing features, supporting the role of US as a useful tool for identifying underlying inflammatory mechanisms in PsA-related pain. Understanding the interaction between peripheral inflammation and central sensitization may guide more personalized and effective pain management strategies.