Dopamine Release Reduced During Acute Migraine

Basal ganglia
Basal ganglia
Acute migraine attacks are associated with a reduction in dopamine release.

Acute migraine attacks are associated with a reduction in dopamine release, according to a study published in Neurology.1

In patients with migraine, structural and functional changes occur in brain regions that are not directly involved in processing pain signals — such as the striatum or basal ganglia — in which dopamine is a major neurotransmitter. A higher prevalence of disorders associated with low dopamine levels (eg, Parkinson disease and restless legs syndrome) is found within the migraine vs non-migraine population, indicating a possible link between dopamine levels and migraine.2,3 In addition, dopamine receptor antagonists have shown effectiveness in treating migraine.4

The role that dopamine plays in acute migraine is unclear, as data examining this relationship are lacking. In the current study, researchers sought to determine the  levels of dopamine released during acute migraine attacks by performing positron emission tomography (PET) scans in migraineurs, both during acute attacks (ictal phase) and the non-headache (interictal) phase.

PET scans were conducted using the [11C]raclopride radiotracer, a tracer specific for the D2/D3 dopamine receptors highly expressed in the striatum. An increase in [11C]raclopride uptake indicates a decrease in dopamine levels. A total of 8 patients with episodic migraine and 8 healthy controls was enrolled in the study. On average, migraine-related pain was considered moderate, with a score of 7 on a 10-point pain scale.

Among migraineurs, the ictal phase was associated with higher [11C]raclopride uptake in the striatum than the interictal phase, suggesting reduced dopamine release during acute attacks. [11C]raclopride uptake at rest was similar in both migraineurs and healthy controls.

The study participants underwent 2 PET sessions: one during a spontaneous migraine ictal phase at rest, followed by a sustained thermal pain threshold challenge to the region of the face innervated by the ophthalmic branch of the trigeminal nerve, eliciting allodynia; and the other during the interictal phase. Migraineurs exhibited decreased [11C]raclopride uptake in the insula during the ictal phase compared with the interictal phase, suggesting an increase in dopamine release during ictal allodynia.

The researchers also found that more chronic migraine disorders and more frequent attacks were associated with lower levels of dopamine release during acute attacks.

Summary and Clinical Applicability

Magnetic resonance imaging (MRI) findings and the association between migraine and dopamine-deficient disorders suggest that dopamine may play an important role in migraine pathophysiology. In this PET-based study, researchers found that endogenous dopamine release is reduced during migraine attacks and increased during cutaneous heat allodynia.

“Although more studies are needed to confirm our findings, this study demonstrates that there is a transient [dopamine] reduction and imbalance in the striatum region and insula during migraine attacks contributing to patients’ pain and discomfort, and increasing their global sensory sensitivity and aversive reactions to environmental stimuli,” the researchers wrote.

Limitations and Disclosures

The study was conducted in a small number of participants (n=16)

The study does not elucidate the mechanisms by which changes in endogenous dopamine release may influence migraine-related pain and symptoms

Alexandre F. DaSilva, DDS, DMedSc, co-founded GeoPain and MoxyTech LLC. The other researchers report no relevant disclosures.

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  1. DaSilva AF, Nascimento TD, Jassar H, et al. Dopamine D2/D3 imbalance during migraine attack and allodynia in vivo. [published online March 29, 2017] Neurology. doi:10.1212/WNL.0000000000003861
  2. Scher AI, Ross GW, Sigurdsson S, et al. Midlife migraine and late-life parkinsonism: AGES-Reykjavik study. Neurology. 2014;83(14):1246-1252. doi:10.1212/WNL.0000000000000840
  3. Cervenka S, Pålhagen SE, Comley RA, et al. Support for dopaminergic hypoactivity in restless legs syndrome: a PET study on D2-receptor binding. Brain. 2006;129(Pt 8):2017-2028.
  4. Marmura MJ. Use of dopamine antagonists in treatment of migraine. Curr Treat Options Neurol. 2012;14(1):27-35. doi:10.1007/s11940-011-0150-9