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.
connexins, cortical spreading depression, gap junctions, tonabersat, trigeminovascular
Durham, P. L., and F. G. Garrett. "Neurological mechanisms of migraine: potential of the gap‐junction modulator tonabersat in prevention of migraine." Cephalalgia 29 (2009): 1-6.