Mediators of Mast Cell as Triggers of Migraine Pain: Comparison of Histamineand Serotonin in Activation of Primary Afferents in Rat Meninges
Meninges surrounding brain have an abundant blood supply, high density of sensory nerves and occupied by a large number of mast cells. In migraine, the most common neurological disorder, activation of the trigeminal nerve fibers in meninges serves as the initial step in the generation of pain signals. A new concept of the neuro-immune synapse suggests that the mediators released from mast cells are able to activate receptors in nearby nerve endings, generating nociceptive spikes. Serotonin and histamine suggested as the putative migraine triggers are the classical mediators secreted during degranulation of mast cells. Our recent studies indicated the leading role of 5-HT3 receptors in robust serotonin-induced activation of primary afferents. However, the role of histamine in the meningeal neuro-immune synapse remained poorly understood. Therefore, by recording spikes from the rat primary afferents in meninges, we investigated the role of histamine as a trigger of migraine pain. We found that out of all tested concentrations, histamine, only in 10 µМ slightly (about 12%) increased the nociceptive activity in the trigeminal nerve. A detailed cluster analysis revealed that the number of fibers reacting to histamine did not exceed 29% and in single fibers, this effect was much weaker than the effect of serotonin. Even a long, 4 h, exposure to histamine did not change the activity of the trigeminal nerve significantly. The results of this study do not exclude the stimulating role of histamine in migraine but suggest that the action of this mast cell mediator, does not involve a significant activation of the trigeminal nerve.