[Gap junctional intercellular communication: a new mechanism in pathophysiology of migraine with aura. Therapeutic applications].
Migraine is a common, recurrent and disabling primary headache disorder, which affects up to 20% of the population. About a third of patients with migraine have attacks with aura, a focal neurological disturbance that manifests itself as visual, sensitive or motor symptoms. Cortical spreading depression, a wave of electrical activity that moves across the cerebral cortex through neuronal-glial cell gap junctions, would be involved in the triggering of migraine aura. Moreover, cortical spreading depression activates perivascular trigeminal afferents in the neocortex, that through central and peripheral reflex, cause inflammatory reaction in the meninges to generate the headache. Tonabersat, a novel benzopyran compound, was selected for clinical trial on the basis of its inhibitory activity on cortical spreading depression and neurogenic inflammation in animal models of migraine. Moreover, tonabersat inhibited trigeminal ganglion neuronal-glial cell gap junctions, suggesting that this compound could prevent peripheral sensitization within the ganglion. In clinical trial, tonabersat showed a preventive effect on attacks of migraine with aura but had no efficacy on non-aura attacks and in the acute treatment of migraine. In conclusion, neuronal-glial cell gap junctional intercellular communication seems to be involved in the pathophysiology of migraine with aura and is emerging as a new promising therapeutic target for prophylactic treatment of patients with chronic attacks.
Institut de physiologie et de biologie cellulaire, FRE CNRS 3511, université de Poitiers, 40 avenue du Recteur-Pineau, Poitiers cedex, France. Denis.Sarrouilhe@univ-poitiers.fr
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D000293:Adolescent; D000328:Adult; D000818:Animals; D001549:Benzamides / Q000627:therapeutic use; D001578:Benzopyrans / Q000627:therapeutic use; D002450:Cell Communication / Q000502:physiology*; D013181:Cortical Spreading Depression / Q000187:drug effects; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008875:Middle Aged; D020325:Migraine with Aura / Q000188:drug therapy* / Q000503:physiopathology* / Q000517:prevention & control; D020078:Neurogenic Inflammation / Q000188:drug therapy / Q000503:physiopathology; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010919:Placebos; D016032:Randomized Controlled Trials as Topic; D012668:Trigeminal Ganglion / Q000503:physiopathology
D001549:Benzamides; D001578:Benzopyrans; D010919:Placebos; C118706:tonabersat