Feasibility, Safety, and Preliminary Efficacy of Intermittent Theta Burst Stimulation Targeting the Left Dorsolateral Prefrontal Cortex in Older Adults with Chronic Low Back Pain with or without Comorbid Chronic Knee Pain: A Pilot Randomized Sham- Controlled Trial

Background Chronic back and knee pain are associated with executive dysfunction in older adults. Intermittent theta burst stimulation (iTBS) over the left dorsolateral prefrontal cortex (L-DLPFC) may modulate pain and cognitive networks, but its application in this population is underexplored. Methods This pilot randomized, double-blind, sham-controlled trial evaluated the feasibility, safety, and preliminary clinical/neural effects of repeated L-DLPFC iTBS in older adults with chronic pain. Thirty participants (aged 60–85 years) were randomized to receive 12 sessions of active or sham iTBS over two weeks. Primary outcomes were feasibility and acceptability. Trial progression viability was evaluated using traffic light system. Secondary outcomes included patient-reported pain intensity, disability, and negative thoughts, alongside executive function performance and task-based functional magnetic resonance imaging. Results The protocol met “Green (Go)” criteria, demonstrating high feasibility and acceptability: the trial achieved an 8.1% recruitment rate, a 93.3% completion rate (6.7% attrition rate), an overall acceptability score (33.1 ± 3.7) significantly above the scale midpoint, and no serious adverse events. Both groups reported reduced chronic low back pain intensity across follow-ups ( P _{FDR−corrected} < 0.001), while knee pain intensity remained unchanged. Unexpectedly, fewer response inhibition errors in executive function were observed primarily in the sham group ( P _{FDR−corrected} = 0.01). Neuroimaging results showed that the active group modulated frontoparietal activity during cognitive switching task. Qualitative interviews identified perceived cognitive/pain benefits, barriers, and optimization suggestions. Conclusions Meeting all pre-specified “Green (Go)” progression criteria confirms that iTBS over the left DLPFC is feasible and well-tolerated for older adults with chronic pain and executive dysfunction. Active stimulation uniquely modulated frontoparietal activity during cognitive switching. Further large-scale RCTs with neuroimaging are warranted to elucidate the neurophysiological basis of treatment efficacy. Trial registration: ClinicalTrials.gov (NCT06709963).