Neuroinflammation in knee osteoarthritis is accompanied by functional reorganization of the S1 cortical knee representation.

Altered somatotopy of primary somatosensory cortex (S1) and elevated brain levels of the neuroinflammation marker Translocator Protein (TSPO) have both been reported in chronic pain, but their association is unknown. To address the functional role of neuroinflammation and its link to cortical reorganization, Positron Emission Tomography/Magnetic Resonance (PET/MR) imaging data acquired with the TSPO radioligand [11C]PBR28 were analyzed for individuals with Knee Osteoarthritis (KOA, n = 22) and healthy controls (HC, n = 20). KOA-related alterations in the S1 somatotopic representation of knee joints (S1KNEE), localized using somatosensory stimulation during functional MR imaging, were evaluated by calculating cortical distance between individual activation peaks and 1) a fiducial vertex located at the ventral base of the postcentral gyrus, near the parietal operculum and 2) the group peak. While the former captures peak localization along the dorsoventral axis of S1 ("dorsoventral distance"), the latter reflects within-group localization variability ("group similarity index"). A Group by Knee side interaction was found for the dorsoventral distance (p = 0.01), indicating a hemispheric asymmetry in KOA (left < right S1KNEE; p < 0.001), not observed in HC. Pain widespreadness correlated with dorsoventral distance for the left S1KNEE (r = 0.55, p = 0.01), while dorsoventral distance correlated with PET signal intensity for the right S1KNEE (r = 0.54, p = 0.03; n = 18). For the right S1KNEE, group similarity index correlated negatively with joint stiffness (r = -0.45, p = 0.04). These results indicate cortical reorganization of the knee representation in KOA and suggest an association with neuroinflammation and clinical metrics for pain and osteoarthritis.