Amygdala and nucleus accumbens activation are associated with treatment choice in knee osteoarthritis: an fMRI study

Pain in knee osteoarthritis (KOA) often shows a limited correlation with radiographic severity, complicating clinical assessment and highlighting the relevance of central pain mechanisms. Functional magnetic resonance imaging (fMRI) enables the investigation of brain regions such as the amygdala and nucleus accumbens, which are increasingly recognized as key components of the affective-motivational dimension of chronic pain and may show differential activation across clinical treatment contexts. This study is part of the HOLOA Project (Clinical and virtual examination of patients for holistic and objective description of the osteoarthritis progression mechanisms).

We conducted a cross-sectional observational study nested within the HOLOA cohort. Thirty-one patients with KOA (20 managed conservatively [CM] and 11 observed in the surgical treatment context) with Kellgren Lawrence (KL) grades 2-3 were included. Participants underwent two fMRI paradigms involving pressure stimulation (Knee Interline and Tibial Surface tests). Clinical assessment included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Pain Catastrophizing Scale (PCS), Hospital Anxiety and Depression Scale (HADS), and Numeric Rating Scale (NRS). Group comparisons and correlation analyses were performed to examine associations between clinical measures and brain activation patterns.

Groups were broadly comparable with no statistically significant differences in demographic or radiographic severity measures. These patients showed higher WOMAC and PCS scores, indicating greater functional impairment and pain catastrophizing. Across the whole cohort, painful stimulation elicited robust activation of classical pain-processing regions, while no significant amygdala or nucleus accumbens activation was observed at the group level. However, nucleus accumbens activity was positively associated with PCS scores. In between-group analyses, patients observed in the surgical treatment context exhibited significant bilateral amygdala activation during Tibial Surface stimulation, which was absent in the conservatively managed group, and reported higher post-test NRS scores.

Limbic system activation and pain catastrophizing were associated with the surgical treatment context in patients with knee osteoarthritis within a similar range of radiographic severity. The observed involvement of the amygdala and nucleus accumbens underscores the relevance of affective-motivational and cognitive processes in chronic KOA pain. These findings support the value of integrating clinical, psychological, and neurobiological perspectives when interpreting symptom burden and treatment context in knee osteoarthritis.