Effects of 10-Hz rTMS, iTBS, and Sham Stimulation on Pain in Fibromyalgia: A Randomized Sham-Controlled Trial

To compare the clinical effects of conventional 10 Hz repetitive transcranial magnetic stimulation (rTMS), intermittent theta-burst stimulation (iTBS), and sham stimulation in fibromyalgia (FM), and to explore associated changes in resting-state functional connectivity.

In this randomized, triple-blind, sham-controlled trial, 45 women with FM were allocated 1:1:1 to receive seven sessions of 10 Hz rTMS (1600 pulses), iTBS (600 pulses), or sham stimulation over the left primary motor cortex. The primary outcome was the proportion of participants achieving a ≥one-point reduction in Numeric Rating Scale pain from baseline to day seven, defined as minimally important pain improvement. The secondary outcomes included daily pain trajectory, Brief Pain Inventory interference, Fibromyalgia Impact Questionnaire scores, and exploratory resting-state functional connectivity.

A ≥one-point pain reduction was observed in 80.0% of the 10 Hz group, 53.3% of the sham group, and 46.7% of the iTBS group. In adjusted modified Poisson regression, 10 Hz rTMS was associated with a higher likelihood of minimally important pain improvement than sham (adjusted RR 1.58; 95% confidence interval [CI], 1.02-2.49; p = 0.045), whereas iTBS was not. In an exploratory sensitivity analysis using a more stringent ≥two-point numeric rating scale reduction threshold, responder rates were lower but preserved the same numeric pattern favoring 10 Hz rTMS over sham and iTBS. Only the 10 Hz group showed significant within-group reductions in pain intensity (p = 0.001) and pain-related interference (p = 0.033). FM impact improved in the 10 Hz and sham groups, without between-group differences. Between-group connectivity comparisons were not significant, but exploratory within-condition analyses after 10 Hz showed increased connectivity between a salience-related supramarginal seed and bilateral sensorimotor or medial parietal regions.

Conventional 10 Hz rTMS was associated with the most consistent pattern of clinical benefit in FM, including a higher adjusted likelihood of minimally important pain improvement and reduced pain-related interference. Exploratory imaging findings suggest possible modulation of salience-related sensorimotor networks but should be interpreted as hypothesis-generating because direct between-group imaging differences were not significant.