Mechanisms underlying migraine chronification

Mamoru Shibata

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


Chronification of migraine occurs in approximately 3% of entire cases annually. Some risk factors, like obesity and affective disorder, exacerbate the migraine disease conditions. The incidence of migraine chronification is dependent on the baseline frequency of migraine attacks. Functional MRI data support that dysfunction of the descending anti-nociceptive systems plays an important role in the development of migraine chronification. Moreover, several studies employing voxel-based morphometry have revealed morphological alterations of gray matter density in various brain regions, some of which are irrelevant to the sensory or limbic systems. It remains to be determined whether such organic changes are either causative of or attributable to migraine chronification. A preclinical study showed that cortical spreading depression can activate matrix metalloproteinase-9, potentially leading to disruption of blood-brain barrier and subsequent parenchymal damage. We demonstrated that TRPV1 (transient receptor potential vanilloid subfamily, member 1) stimulation in the trigeminal nociceptors induces morphological changes of microglia and astrocytes in the trigeminal nucleus caudalis. Recently, botulinum neurotoxin type-A (BoNT-A) has been approved for patients with chronic migraine. The primary action of BoNT-A is inhibition of regulated exocytosis at the peripheral nerve terminals, raising the possibility that certain peripheral factors are implicated in the development of migraine chronification.

Original languageEnglish
Pages (from-to)1012-1013
Number of pages2
JournalClinical Neurology
Issue number11
Publication statusPublished - 2012


  • Botulinum neurotoxin type-A (BoNT-A)
  • Chronic migraine
  • Descending anti-nociceptive system
  • Member 1)
  • Migraine chronification
  • TRPV1 (transient receptor potential vanilloid subfamily

ASJC Scopus subject areas

  • Clinical Neurology


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