Pathophysiological Bases of Comorbidity in Migraine

Abstract

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.

Keywords: CNS disorders; energetic balance; migraine threshold; thalamocortical network dysexcitability; trigeminovascular system.

Figure 1

Schematic representation of the pathophysiological model of bidirectional comorbidity between migraine and other medical conditions. A biological susceptibility, constituted by both nuclear and mitochondrial genomic peculiarities, can predispose to different clinical pathological conditions, to the propensity to some physiological mechanisms, and to the lower the activation threshold of some brain structures. Several pathologies can be comorbid with migraine, including neurological, psychiatric, cardio- and cerebrovascular, gastrointestinal, metaboloendocrine, painful, and immunological conditions. The variable combination of thalamocortical network dysexcitability, of multi-organ transient or persistent pro-inflammatory state, and of disproportionate energetic needs induced and promoted by the additive comorbid pathologies may be causative mechanistic factors of the activation of an ample defensive system that includes the trigeminovascular system in conjunction with the neuroendocrine hypothalamic system.