Does central nervous system dysfunction underlie patellofemoral pain in young females? Examining brain functional connectivity in association with patient-reported outcomes.

Patellofemoral pain (PFP) is defined as retro- or peri-patellar knee pain without a clear structural abnormality. Unfortunately, many current treatment approaches fail to provide long-term pain relief, potentially due to an incomplete understanding of pain-disrupted sensorimotor dysfunction within the central nervous system. The purposes of this study were to evaluate brain functional connectivity in participants with and without PFP, and to determine the relationship between altered brain functional connectivity in association with patient-reported outcomes. Young female patients with PFP (n = 15; 14.3 ± 3.2 years) completed resting-state functional magnetic resonance imaging (rs-fMRI) and patient-reported outcome measures. Each patient with PFP was matched with two controls (n = 30, 15.5 ± 1.4 years) who also completed identical rs-fMRI testing. Six bilateral seeds important for pain and sensorimotor control were created, and seed-to-voxel analyses were conducted to compare functional connectivity between the two groups, as well as to determine the relationship between connectivity alterations and patient-reported outcomes. Relative to controls, patients with PFP exhibited altered functional connectivity between regions important for pain, psychological functioning, and sensorimotor control, and the connectivity alterations were related to perceived disability, dysfunction, and kinesiophobia. The present results support emergent evidence that PFP is not localized to structural knee dysfunction, but may actually be resultant to altered central neural processes. Clinical significance: These data provide potential neuro-therapeutic targets for novel therapies aimed to reorganize neural processes, improve neuromuscular function, and restore an active pain-free lifestyle in young females with PFP.