Neurological mechanisms of migraine: potential of the gap-junction modulator tonabersat in prevention of migraine.
Migraine is a neurovascular disorder characterized by recurrent episodic headaches, and is caused by abnormal processing of sensory information due to peripheral and/or central sensitization. The exact pathophysiological mechanism underlying migraine is not fully understood; however, cortical spreading depression (CSD) is thought to provide the basis for migraine aura and may serve as a trigger of migraine pain. CSD depends on neuronal-glial cell communication, which is mediated by intercellular transfer of messengers through connexin-containing gap junctions, as well as messengers released into the extracellular space by non-junctional connexin-containing hemichannels. These processes are believed to be important in peripheral sensitization within the trigeminal ganglion and to lead to central sensitization. The novel benzopyran compound tonabersat binds selectively to a unique site in the brain. In preclinical studies, tonabersat markedly reduced CSD and CSD-associated events and inhibited gap-junction communication between neurons and satellite glial cells in the trigeminal ganglion. Together, these findings suggest that tonabersat should have clinical application in preventing migraine attacks.
Durham
P L
PL
Center for Biomedical and Life Sciences, Missouri State University, Springfield, MO 65897, USA. pauldurham@missouristate.edu
Garrett
F G
FG
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D013181:Cortical Spreading Depression / Q000502:physiology; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008881:Migraine Disorders / Q000503:physiopathology* / Q000628:therapy*
D000700:Analgesics; D001549:Benzamides; D001578:Benzopyrans; C118706:tonabersat