Investigation of predictors of pain relief with high-frequency repetitive motor cortex transcranial magnetic stimulation among people with fibromyalgia

OBJECTIVES: To identify baseline predictors of clinical response to the primary motor cortex high-frequency repetitive transcranial magnetic stimulation (M1 HF-rTMS) in patients with fibromyalgia. MATERIALS AND METHODS: We performed a secondary analysis of 32 women with fibromyalgia from a randomized, double-blind, sham-controlled international multicenter trial registered at clinicaltrials.gov (NCT03658694). Enrolled participants received active or HF-rTMS-over the primary motor cortex (M1). Baseline demographic data, psychological assessments (Hospital Anxiety and Depression Scale, Brief Pain Inventory, Fibromyalgia Impact Questionnaire, Toronto Alexithymia Scale, and Interoception Questionnaire), psychophysical measures (Conditioned Pain Modulation), and structural brain MRI variables were collected and analyzed. Responders were defined as patients who achieved a ≥ 50 % reduction in pain on a numerical rating scale eight weeks after treatment. Associations between baseline variables and response were analyzed using Wilcoxon Rank Sum tests, chi-square tests, and logistic regression where appropriate. RESULTS: At the end of the treatment period, 15 out of 32 participants (47 %) in the active M1 HF-rTMS group and 7 out of 30 (23 %) in the sham group achieved ≥50 % reduction in pain. None of the baseline demographic, clinical, psychological, psychophysical, or neuroimaging variables evaluated were significantly associated with clinical response to M1 HF-rTMS. Although M1 HF-rTMS induced significant antinociceptive effects measured by psychophysical assessments (heat pain threshold), these effects did not predict clinical outcomes. CONCLUSIONS: No clear baseline predictors of response to M1 HF-rTMS were identified in patients with fibromyalgia, emphasizing the heterogeneity and complexity of the disorder. Further research incorporating larger samples and additional biomarkers is necessary to establish individualized prediction strategies for M1 HF-rTMS therapy in fibromyalgia.