While high-frequency transcranial magnetic stimulation (HF-rTMS) is now included in the armamentarium to treat chronic neuropathic pain (NP), direct-current anodal stimulation (a-tDCS) to the same cortical targets may represent a valuable alternative in terms of feasibility and cost. Here we performed a head-to-head, randomized, single-blinded, cross-over comparison of HF-rTMS versus a-tDCS over the motor cortex in 56 patients with drug-resistant NP, who received 5 daily sessions of each procedure, with a washout of at least 4 weeks. Daily scores of pain, sleep, and fatigue were obtained during 5 consecutive weeks, and functional magnetic resonance imaging (fMRI) to a motor task was performed in a subgroup of 31 patients. The percentage of responders, defined by a reduction in pain scores of > 2 SDs from pre-stimulus levels, was similar to both techniques (42.0% vs. 42.3%), while the magnitude of "best pain relief" was significantly skewed towards rTMS. Mean pain ratings in responders decreased by 32.6% (rTMS) and 29.6% (tDCS), with half of them being sensitive to only one technique. Movement-related fMRI showed significant activations in motor and premotor areas, which did not change after 5 days of stimulation, and did not discriminate responders from non-responders. Both HF-rTMS and a-tDCS showed efficacy at 1 month in drug-resistant NP, with magnitude of relief slightly favoring rTMS. Since a significant proportion of patients responded to one procedure only, both modalities should be tested before declaring a patient as unresponsive.
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