711: Brain Activity Associated with Walking Pain Versus Pain Appraisal at Rest in Knee Osteoarthritis

Topic: Experimental (Non-clinical) Human Studies
Subtopic: Pain Category (ICD-11), Chronic primary musculoskeletal pain, Assessment and Measurement of Pain/Nociception, Imaging (e.g. fMRI, PET, MRS)

Background and Aims: Although preclinical models implicate brain processing in knee osteoarthritis (OA), brain mechanisms in patients are less understood. This is in part due to limitations in commonly used noninvasive brain imaging techniques, which rely on static supine positioning, a clear mismatch with clinical knee OA pain which is exacerbated by weight-bearing and ambulation. Functional near-infrared spectroscopy (fNIRS) shows promise as an ambulatory noninvasive brain imaging modality. However, nonneural hemodynamic changes during exercise complicate the interpretation of fNIRS signals. The aim of this study was to isolate pain-specific neural correlates of clinically relevant knee osteoarthritis pain during walking.

Methods: We measured frontal and somatomotor cortical activity with fNIRS during the 6-minute walk test (6MWT) in knee OA patients (n=54) and controls (n=27). Knee pain intensity was assessed at the start of the study visit at rest using a numeric rating scale (NRS, 0-10) as is standard in clinical practice and research. Then, knee pain intensity was assessed immediately before and after the walk (NRS, 0-10) with walking-induced pain defined as any increase in pain. FNIRS signals from the beginning and end of the 6MWT were preprocessed to reduce movement and cardiopulmonary noise and entered into a whole-montage connectivity analysis.

Results: Connectivity increased globally from the beginning to the end of the 6MWT, likely reflecting physiologic effects of exercise. To isolate pain-specific effects, the knee OA group was subdivided by standard pain assessment into mild and moderate-severe pain groups and by the presence of walking-induced pain increases. Participants with decreases in pain were excluded (n= 5). Permutation testing based on subgroup membership further controlled for exercise effects. While walking-induced pain was associated with robust left dorsolateral prefrontal cortex (dlPFC) reductions in connectivity (pain increase – stable: T=-11.6, p(adj) < 0.001), there were no statistically significant effects using standard pain assessment subgroupings.

Conclusions: In a large sample of participants performing a standard walking task, we found cortical connectivity varies based on walking knee pain but not on pain appraisals at rest. We observed a relative reduction in left dlPFC connectivity in knee OA participants with walking-induced pain. Remarkably, results were null when subdividing knee OA participants by pain intensity reported at the start of the visit, which is standard in clinical practice and research. This suggests mechanistic differences in movement-evoked pain versus pain intensity appraisals at rest. Future emphasis on movement-evoked pain and associated neural underpinnings may advance knee OA pain care.

References: none

Presenting Author: Benedict Alter
Submitting Author: Benedict Alter

Senior Author: Benedict Alter

IASP 2026 Global Year theme of Neuropathic Pain: No

• Sarah Margerison: PhD - University of Pittsburgh
• Destin Rothe: MS - University of Pittsburgh
• Maya Maurer: MS - University of Pittsburgh
• Hendrik Santosa: PhD - University of Pittsburgh
• Theodore Huppert: PhD - University of Pittsburgh
• Ajay Wasan: MD, MS - University of Pittsburgh
• Benedict Alter: MD, PhD - University of Pittsburgh