Reduced habituation of the nociceptive blink reflex (NBR) is considered a trait marker for genetic predisposition to migraine. In this open-label randomized controlled study, we aimed to test the efficacy of a biofeedback training based on learning of habituation of the NBR (NBR biofeedback) compared with pharmacological (topiramate) treatment and NBR biofeedback plus topiramate treatment in a cohort of migraine without aura patients eligible for prophylaxis. Thirty-three migraine patients were randomly assigned to three months of treatment with: 1) NBR biofeedback, 2) NBR biofeedback plus topiramate 50 mg (b.i.d.), or 3) topiramate 50 mg (b.i.d.). Frequency of headache and disability changes were the main study outcomes. Anxiety, depression, sleep, fatigue, quality of life, allodynia and pericranial tenderness were also evaluated. NBR biofeedback reduced the R2 area, without improving R2 habituation. However, it reduced the frequency of headache and disability, similarly to the combined treatment and topiramate alone. Reduced habituation of the NBR is a stable neurophysiological pattern, scarcely modifiable by learning procedures. Training methods able to act on stress-related responses may modulate cortical mechanisms inducing migraine onset and trigeminal activation under stressful trigger factors.