Involvement of the cerebellum in migraine

Abstract

Migraine is a disabling neurological disease characterized by moderate or severe headaches and accompanied by sensory abnormalities, e.g., photophobia, allodynia, and vertigo. It affects approximately 15% of people worldwide. Despite advancements in current migraine therapeutics, mechanisms underlying migraine remain elusive. Within the central nervous system, studies have hinted that the cerebellum may play an important sensory integrative role in migraine. More specifically, the cerebellum has been proposed to modulate pain processing, and imaging studies have revealed cerebellar alterations in migraine patients. This review aims to summarize the clinical and preclinical studies that link the cerebellum to migraine. We will first discuss cerebellar roles in pain modulation, including cerebellar neuronal connections with pain-related brain regions. Next, we will review cerebellar symptoms and cerebellar imaging data in migraine patients. Lastly, we will highlight the possible roles of the neuropeptide calcitonin gene-related peptide (CGRP) in migraine symptoms, including preclinical cerebellar studies in animal models of migraine.

Brain structural and functional abnormalities in patients with tension‐type headache: A systematic review of magnetic resonance imaging studies

“…Consequently, the observed gray matter changes in the cerebellum could be linked to variations in pain severity, and mirroring patterns observed in migraines (Ruscheweyh et al., 2014). Earlier studies have indicated both decreases and increases in cerebellar gray matter volume among individuals with migraines, consistent with the findings from our included studies involving TTH patients (Wang, Tutt, et al., 2022). To gain a more comprehensive understanding of the role of the cerebellum in TTH, future preclinical and clinical studies on cerebellar changes in individuals with TTH should be conducted.…”

Structural connectome changes in episodic migraine: the role of the cerebellum

“…Therefore, the increased connectivity between the cerebellum and other regions could be indicative of a dysfunctional negative feedback loop in which the thalamus is not sensing the inhibitory signal (31). These connectivity results could be indicative of the importance of the cerebellum in the modulation of migraine possibly through the modulation of calcitonin gene-related peptide (CGRP) (11, 14). CGRP modulates nociception and assists in the onset of migraine, and thus it might play a role in reshaping connectivity and stabilizing synapses in the cerebellar circuitry (33, 34).…”

“…Critically, although the cerebellum has an important role in pain processing (14), to our knowledge no study of structural connectivity using tractography in migraine has included it.…”

“…Critically, although the cerebellum has an important role in pain processing (14), to our knowledge no study of structural connectivity using tractography in migraine has included it. Moreover, despite the accumulation of evidence supporting structural connectivity alterations in migraine, previous studies either focused entirely on chronic migraine, combined the chronic and episodic forms of migraine, or mixed patients with and without aura (3,4,10).…”

Migraine treatment with GON blockade at the level of C2: The tip of the iceberg and the submerged portion

“…In conclusion, while C2 GON blockade has demonstrated some superiority over distal GON blockade for the treatment of migraine, we do not anticipate it having a significant impact on clinical practice. However, the fact that this blockade can cause cerebellar side effects in migraine patients may support further examination of the role of residual cerebellum in migraine pathophysiology, potentially leading to new target regions for pharmacological interventions [16][17][18] . This potential avenue of research could open up new horizons for treating migraine and could be seen as the most important benefit of C2 GON blockade for migraine patients.…”