Development and distribution of PAG-immunoreactive neurons in the central pathway of trigeminal proprioception of the rat brainstem*

Objective: To investigate the development and distribution of phosphate-activated glutaminase like immunoreactive (PAG-LI) neurons in the central pathway of trigeminal proprioception of the rat brainstem. Methods: The immunohistochemitry techniques were used. Results: (1) At embryonic day 17 (E17), PAG-LI neurons were initially observed in the mesencephalic trigeminal nucleus (Vme). All PAG-LI neurons were large round neurons with moderate immunostaining. The immunoreactivity grew intense and attained adult-like pattern at P10. (2) Not until postnatal day 10 (P10) did a few PAG-LI neurons appear in the area ven-tral to the motor trigeminal nucleus (AVM) and area dorsal to the superior olivery nucleus (ADO), and not until P12 in the dorsomedial part of the subnucleus oralis of the spinal trigeminal nucleus (Vodm) and dorso-medial part of the principal sensory trigeminal nucleus (Vpdm). As development proceeded, more and more neurons in them were immunostained, and some PAG-LI neurons were detected in the lateral reticular forma-tion adjacent to the Vodm(LRF)and the caudolateral part of the supratrigeminal nucleus (Vsup-CL) at P21. Conclusion: In the central pathway of trigeminal proprioception of the rat brainstem, PAG-LI neurons ap-peared during two stages: The first stage from E17 to P10, PAG-LI neurons appeared in the Vme and reached adult-like pattern; the second stage from P10 to P21, PAG-LI neurons appeared in the Vodm, LRF, Vpdm, Vsup-CL, ADO, AVM and gradually reached adult-like pattern. This might be relative to the estab-lishment of jaw movement patterns.

Role of cortical spreading depression in the pathophysiology of migraine

A migraine is a recurring neurological disorder characterized by unilateral, intense, and pulsatile headaches. In one-third of migraine patients, the attacks are preceded by a visual aura, such as a slowly-propagating scintillating scotoma. Migraine aura is thought to be a result of the neurovascular phenomenon of cortical spreading depression （SD）, a self-propagating wave of depolarization that spreads across the cerebral cortex. Several animal experiments have demonstrated that cortical SD causes intracranial neurogenic inflammation around the meningeal blood vessels, such as plasma protein extravasation and pro-inflammatory peptide release. Cortical SD has also been reported to activate both peripheral and central trigeminal nociceptive pathways. Although several issues remain to be resolved, recent evidence suggests that cortical SD could be the initial trigger of intracranial neurogenic inflammation, which then contributes to migraine headaches via subsequent activation of trigeminal afferents.