Repetitive GON Blockade for Menstrual Migraine

Menstrual migraine (MM) is a highly prevalent and challenging migraine subtype triggered by fluctuations in estrogen and progesterone levels, particularly estrogen withdrawal during the perimenstrual period

* This hormonal withdrawal sensitizes the trigeminovascular system and promotes the release of neuropeptides such as calcitonin gene-related peptide (CGRP)
* Currently, there are no licensed prophylactic medications specifically developed for MM, making alternative and non-systemic treatments necessary

This study investigates the efficacy of a targeted peripheral neuromodulation approach using bilateral greater occipital nerve (GON) blockade. The underlying clinical rationale is that GON blockade timed to the perimenstrual period can modulate nociceptive transmission at the trigeminocervical complex (TCC) and decrease peripheral nerve excitability, thereby limiting the impact of cyclic hormonal fluctuations on the trigeminovascular system

. In this trial, a Latin square experimental design is utilized to ensure balanced randomization between the active treatment and placebo groups

* Unlike single-injection protocols, the intervention is specifically synchronized with the patients' menstrual cycles, involving injections twice a month over a three-month period (seven days before menstruation and on the first day of menstruation)
* By evaluating this specific timing and repetitive protocol, the study aims to establish whether perimenstrual-targeted GON blockade can serve as an effective, non-systemic, short-term prophylactic strategy for patients suffering from this refractory migraine subtype.

• 0.5% bupivacaine (Drug): Bilateral greater occipital nerve (GON) blockade using a local anesthetic.
• Normal Saline (Other): Bilateral greater occipital nerve (GON) blockade using placebo (normal saline).

Primary outcomes

• Change in headache severity evaluated using the Visual Analog Scale (VAS) [Baseline, Month 3, and Month 6]: Headache severity measured by VAS.

Secondary outcomes

• Change in monthly migraine attack frequency [Baseline, Month 3, and Month 6]
• Change in number of headache days per month [Baseline, Month 3, and Month 6]
• Change in mean attack duration in hours [Baseline, Month 3, and Month 6]
• Change in monthly analgesic consumption [Baseline, Month 3, and Month 6]
• Change in Migraine Disability Assessment (MIDAS) scores [Baseline, Month 3, and Month 6]

Sex: Female, ages: 18 Years to 50 Years

Inclusion Criteria:

* Diagnosed with pure menstrual migraine or menstrually related migraine according to the International Classification of Headache Disorders, 3rd edition (ICHD-3) diagnostic criteria.
* A documented history of migraine attacks during the perimenstrual period (between days -2 and +3 relative to the onset of menstruation) in at least two of the last three menstrual cycles.

Exclusion Criteria:

* Diagnosis of chronic migraine.
* Presence of an additional primary or secondary headache disorder.
* Pregnant or lactating.
* Known hypersensitivity to local anesthetics.
* Received an occipital nerve blockade within the last three months.
* Presence of a significant neurological or systemic disease that could affect the outcome evaluation.

• Cetin G, Totuk O, Cetin OE, Demir S, Sahin S. Evaluation of the effectiveness of greater occipital nerve blockade in menstrual migraine. BMC Neurol. 2025 Feb 13;25(1):62. doi: 10.1186/s12883-025-04070-2. PMID 39948478