Background: In migraine, high rate repetitive transcranial magnetic stimulation (rTMS) has been reported to be effective, and β endorphin (BE) may have a role in headache relief.

Objective: To report the role of BE and its μ (MOR) and δ opioid receptors (DOR) in headache relief following high rate rTMS in migraine.

Methods: Ninety-three migraine patients having more than 4 attacks per month were included. 10 Hz rTMS (600 pulses in 10 trains) was delivered to left motor cortex; 3 sessions to 24 (group 1), 1 session to 22 (group II) and sham stimulation to 47 patients (group III). Plasma BE, and MOR and DOR RNA expressions were measured before and third session of rTMS. The improvement in headache frequency and severity was assessed at 1month.

Results: Plasma BE level was lower in the migraine patients compared to controls (P = 0.01). Post-stimulation BE level was higher in group I compared to group III (P = 0.02). The responders had higher BE level than non-responders (P = 0.004). Post-stimulation BE level above 4 ng/ml was associated with improvement in headache frequency in 43 (81.1%) patients, whereas only 23 (57.5%) improved if BE was below 4 ng/ml (P = 0.02) irrespective of type of rTMS.

Conclusion: 10 Hz rTMS relieves headache by increasing BE level. BE level above 4 ng/ml is critical in headache relief irrespective of type of rTMS.