Serotonergic mechanisms in the migraine brain – a systematic review

Abstract

Background Migraine is one of the most common and disabling of all medical conditions, affecting 16% of the general population, causing huge socioeconomic costs globally. Current available treatment options are inadequate. Serotonin is a key molecule in the neurobiology of migraine, but the exact role of brain serotonergic mechanisms remains a matter of controversy. Methods We systematically searched PubMed for studies investigating the serotonergic system in the migraine brain by either molecular neuroimaging or electrophysiological methods. Results The literature search resulted in 59 papers, of which 13 were eligible for review. The reviewed papers collectively support the notion that migraine patients have alterations in serotonergic neurotransmission. Most likely, migraine patients have a low cerebral serotonin level between attacks, which elevates during a migraine attack. Conclusion This review suggests that novel methods of investigating the serotonergic system in the migraine brain are warranted. Uncovering the serotonergic mechanisms in migraine pathophysiology could prove useful for the development of future migraine drugs.

Serotonin and Neuropeptides in Blood From Episodic and Chronic Migraine and Cluster Headache Patients in Case‐Control and Case‐Crossover Settings: A Systematic Review and Meta‐Analysis

“…Although an unaltered 5‐HT blood level is observed in some strata, altered 5‐HT levels might exist in the brain 62 . 5‐HT in blood is mainly located in platelets but upon release, 5‐HT is rapidly broken down to 5‐hydroxyindoleacetic acid (5‐HIAA) which is often used as a surrogate measure.…”

Modulation of brainstem activity and connectivity by respiratory-gated auricular vagal afferent nerve stimulation in migraine patients

“…Hypersensitization of the brainstem trigeminal sensory complex may underlie the primary brain dysfunction in migraine [1; 10; 58; 71], leading to brainstem-mediated upregulation of cortical excitability [14; 40]. Therapeutic options have targeted brainstem neuromodulatory centers, including serotonergic (raphe nuclei) and noradrenergic (locus coeruleus) nuclei [19; 63], via dihydroergotamine, triptans, and other 5HT1B/1D agonists [21; 41; 62]. More recently, novel neuromodulation therapies have been proposed [44; 65].…”

Vomiting and migraine‐related clinical parameters in pediatric migraine

“…The migraine group had worse findings for all parameters, suggesting that autonomic dysfunction is either a risk factor for migraine headaches or a consequence of frequent disabling attacks. Furthermore, migraine‐related alterations in cerebral serotonergic neurotransmission were reported by Deen et al, who found that in patients with migraine, cerebral 5‐HT3 level is low between attacks and rises during attacks. The role of SP in migraine was illustrated in a series of innovative experimental migraine models.…”