Evaluation of c-Fos immunoreactivity in the rat brainstem nuclei relevant in migraine pathogenesis after electrical stimulation of the trigeminal ganglion

Migraine is a common neurological condition, causing high disability, but the pathomechanism of the disease is not yet fully understood. Activation of the trigeminovascular system could play a crucial role in the manifestation of the symptoms, but initial step of this activation remains unknown. Functional imaging studies have revealed that certain brainstem areas, referred to as migraine generators, are activated during a migraine attack, including the dorsal raphe, the periaqueductal gray, the locus coeruleus, and the nucleus raphe magnus. However, the studies performed to date have not demonstrated whether this activation is a trigger or a consequence of the migraine attack. With the aim of evaluating the functional relationship between activation of the trigeminal system and migraine generators, we examined the changes in c-Fos immunoreactivity in the above-mentioned nuclei after stimulation of the trigeminal ganglion, an animal model for trigeminovascular activation. The stimulation led to significant increases in the number of c-Fos immunoreactive cells in the nucleus raphe magnus and in the caudal part of the spinal trigeminal nucleus, 2 and 4 h after the stimulation. Activation of the trigeminal system failed to exhibit uniform activation of the brain stem nuclei related to migraine. Our results suggest that the activation of the trigeminal system in the rat by electrical stimulation of the trigeminal ganglion leads to the activation of the descending pain modulatory system, but not to the activation of "migraine generator" nuclei. Therefore, the activity pattern seen in functional studies may reflect a unique feature, exclusively present in migraine.