Effects of 24-Hydroxycholesterol on the ATP-Induced Trigeminal Nerve Electrical Activity and the Mast Cells Degranulation

The trigeminovascular system plays a pivotal role in the generation of nociceptive activity, which underlies pain in migraine and includes trigeminal nerve afferents, dura mater vessels, and mast cells. Adenosine triphosphate (ATP) is one of the main mediators of the interaction between vessels, nerve endings, and mast cells. ATP activates P2X3 receptors of trigeminal nerve afferents and P2X7 receptors of mast cells. 24-Hydroxycholesterol is the primary brain cholesterol metabolite synthesized by neurons and is capable of freely entering the bloodstream by crossing the blood–brain barrier. The purpose of this study was to examine the impact of 24-hydroxycholesterol on the electrical activity of trigeminal nerve afferents triggered by ATP application and on the mast cells degranulation in rat brain meninges. The electrical activity of the trigeminal nerve was recorded using an extracellular electrode in a rat hemiskull preparation, mast cells were stained with toluidine blue. 24-Hydroxycholesterol had no direct effect on the frequency of action potentials of trigeminal nerve but suppressed the response triggered by ATP application. Furthermore, incubation of meninges in 24-hydroxycholesterol resulted in a reduction in mast cell degranulation in response to ATP. Therefore, 24-hydroxycholesterol prevented the activation of trigeminal afferents either directly by reducing the activity of ionotropic ATP receptors or indirectly by stabilizing mast cells.