The rapid influx of cerebral spinal fluid (CSF) and protein solutes released during cortical spreading depression (CSD) in the brain activates neurons to trigger aural migraine headaches, according to a new mouse study. The findings identify a novel non-synaptic signaling mechanism between the brain and peripheral sensory system important for migraine. They also suggest potential pharmacological targets for treating the painful disorder.
Migraine with aura, or an aural migraine, is a distinct headache disorder that can include sensory disturbances, such as hearing- or vision-related symptoms that precede onset of headache pain. During the aura phase, it is believed that waves of CSD are spontaneously triggered in the cerebral cortex or cerebellum, which, in turn, lead to activation of pain receptors (nociceptors) in the peripheral nervous system (PNS). Previous research has suggested that CSD events release small molecules through the CSF that activate sensory nerve endings in the external tissues of the CNS (central nervous system), "outside" of the blood-brain barrier.
These nerve endings are not exposed to CSF. How pathological CSD events in the cortex trigger the activation of peripheral nociceptors outside the brain remains poorly understood. Using a combination of proteomic, histological, imaging, and functional approaches in a mouse model of classical migraine, Martin Rasmussen and colleagues identified a signaling pathway between the CNS and PNS at the trigeminal gang.