Impact of Intermittent Theta Burst Stimulation on Pain Relief and Brain Connectivity in Chronic Low Back Pain

BACKGROUND: This randomised clinical trial investigated the effect of intermittent theta burst stimulation (iTBS) over the dorsolateral prefrontal cortex (DLPFC) on pain alleviation in patients with chronic low back pain (CLBP) and its underlying mechanisms. METHODS: Forty CLBP patients were randomly assigned to receive either active or sham iTBS combined with core stability exercise. Pain assessments were completed before and after the intervention. Eleven patients from each group underwent resting-state functional magnetic resonance imaging scans pre- and post-intervention to analyse DLPFC activation and connectivity with other brain regions. RESULTS: The active iTBS group had a greater pain reduction than the sham group (p = 0.05, 95% CI: -0.009 to 1.109). In the active and sham groups, 80% (16/20) and 40% (8/20) reached the minimal clinically important difference, respectively, with a number needed to treat of 2.5. For the Fear-Avoidance Beliefs Questionnaire, there was a significant difference between the two groups (p = 0.011, r = 0.40). The active iTBS group showed a significantly enhanced functional connectivity between the left DLPFC and the right cerebellum, as well as both occipital gyri (voxel-level, p < 0.001; cluster-level familywise error rate, p < 0.01). Spearman's correlation analysis showed a significant negative correlation between Numerical Rating Scale and the FC of the left DLPFC and the right cerebellum (rho = -0.55, p = 0.008), the right (rho = -0.439, p = 0.01), and left occipital gyri (rho = -0.45, p = 0.034). CONCLUSION: iTBS may alleviate pain in CLBP patients by enhancing DLPFC connectivity with the cerebellum and occipital gyrus. SIGNIFICANCE: This study showed a facilitatory effect of iTBS on alleviating CLBP, which might be modulated by brain functional connectivity. Trial Registration Chinese Clinical Trial Registry: ChiCTR2200064899.