Pathophysiological Bases of Comorbidity in Migraine

Claudia Altamura, Ilenia Corbelli, Marina de Tommaso, Cherubino Di Lorenzo, Giorgio Di Lorenzo, Antonio Di Renzo, Massimo Filippi, Tommaso B. Jannini, Roberta Messina, Pasquale Parisi, Vincenzo Parisi, Francesco Pierelli, Innocenzo Rainero, Umberto Raucci, Elisa Rubino, Paola Sarchielli, Linxin Li, Fabrizio Vernieri, Catello Vollono, Gianluca Coppola

Research output: Contribution to journalReview articlepeer-review


Despite that it is commonly accepted that migraine is a disorder of the nervous system with a prominent genetic basis, it is comorbid with a plethora of medical conditions. Several studies have found bidirectional comorbidity between migraine and different disorders including neurological, psychiatric, cardio- and cerebrovascular, gastrointestinal, metaboloendocrine, and immunological conditions. Each of these has its own genetic load and shares some common characteristics with migraine. The bidirectional mechanisms that are likely to underlie this extensive comorbidity between migraine and other diseases are manifold. Comorbid pathologies can induce and promote thalamocortical network dysexcitability, multi-organ transient or persistent pro-inflammatory state, and disproportionate energetic needs in a variable combination, which in turn may be causative mechanisms of the activation of an ample defensive system with includes the trigeminovascular system in conjunction with the neuroendocrine hypothalamic system. This strategy is designed to maintain brain homeostasis by regulating homeostatic needs, such as normal subcortico-cortical excitability, energy balance, osmoregulation, and emotional response. In this light, the treatment of migraine should always involves a multidisciplinary approach, aimed at identifying and, if necessary, eliminating possible risk and comorbidity factors.

Original languageEnglish
Article number640574
JournalFrontiers in Human Neuroscience
Publication statusPublished - Apr 20 2021


  • CNS disorders
  • energetic balance
  • migraine threshold
  • thalamocortical network dysexcitability
  • trigeminovascular system

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology
  • Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry
  • Behavioral Neuroscience


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