A new path to migraine

Abstract

Migraine pain is believed to result from the activation of pain receptors (nociceptors) after the cortical spreading depression (CSD) that is associated with the aura phase of migraine (1). Previous studies have demonstrated that preclinical CSD events release small molecules through the cerebrospinal fluid (CSF) that activate and sensitize afferent trigeminal fibers within the meninges (2, 3). However, it has been thought that trigeminal ganglia reside “outside” the blood-brain barrier and hence are not directly exposed to CSF (4). On page 80 of this issue, Rasmussen et al. (5) show in a mouse model of migraine that after CSD, subarachnoid CSF carries signals from the cortex directly to cell bodies in the trigeminal ganglia, where they activate nociceptors through a pathway that bypasses meningeal trigeminal afferents. The demonstration that the trigeminal ganglia lies within the blood-brain barrier and the identification of the signals that connect aura and headache may provide a new path for preventing and treating migraine.